Autoimmune Antibodies

Description

RELATED APPLICATIONS

This application claims the benefit of EP Application No. 12171126.1, filed Jun. 7, 2012. All the teachings of the above-referenced application is incorporated herein by reference.

SEQUENCE LISTING

The instant application contains a Sequence Listing which has been submitted in ASCII format via EFS-Web and is hereby incorporated by reference in its entirety. Said ASCII copy, created on Jun. 3, 2013, is named P4928SeqList.txt and is 128,129 bytes in size.

FIELD OF THE INVENTION

The present invention provides methods for identifying patients diagnosed with non-small cell lung cancer who will most benefit from treatment with erlotinib comprising detecting autoantibodies in blood serum of said patients.

BACKGROUND OF THE INVENTION

Tarceva® is an orally active, potent, inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase (TKI).

Erlotinib hydrochloride is the active ingredient in Tarceva®, which is approved as single agent treatment for patients with advanced non-small cell lung cancer (NSCLC) after treatment with chemotherapy, as maintenance treatment for patients not progressing during chemotherapy (1^stline maintenance) or after failure of chemotherapy (2^nd/3^rdline maintenance). Tarceva® is also approved as first line treatment for patients whose tumor harbors an EGFR activating mutation in the EU.

Expression of unusual proteins is common in cancer and viral infection. The mammalian immune system contains a specialized arm that recognizes proteins induced by cellular transformation (neo-antigens) and effectively eliminates cells that express these neo-antigens against which tolerance has not established during development. This arm of the immune system is thought to be effective against viral infections, spontaneous chromosomal and genomic rearrangements caused by errors of the cell division machinery, or carcinogen-induced transforming mutations. While the initial cytotoxic immune response—which is mediated by the recognition of the unusual proteins displayed on MHCI complexes by CD8⁺ T-cells—is fast and effective, a sustained response against virus infections or aberrant cellular clones requires the co-stimulatory effect of CD4⁺ T-helper cells which are activated after presentation of extracellular peptides (which can stem from cells lysed in the first phase of the cytotoxic immune response) via MHCII complexes of professional antigen presenting cells. Additionally, these cells are able to induce a lasting B-cell response and antibodies to viral or aberrant proteins. The infiltration of a tumor with large numbers of CD8⁺ T-cells has shown to be a better prognostic marker than traditional tumor staging in colorectal cancer (Koizumi, Hojo et al. 2007¹), and it has been associated with favorable prognosis in almost all major solid carcinomas independently of cancer cell type. ¹Koizumi, K., S. Hojo, et al. (2007). “Chemokine receptors in cancer metastasis and cancer cell-derived chemokines in host immune response.” Cancer Science 98(11): 1652-1658

Autoantibodies are well known diagnostic entities in cancer. Many cancer autoantibodies are proteins that are normally expressed in embryonic tissues and therefore represent a “foreign” protein against which immune tolerance is not established. The shedding of these proteins to the bloodstream late in cancer history leads to a humoral immune response. A typical example is the common cancer marker CEA (cancer embryonic antigen). Tumors frequently exhibit faulty protein processing. Prominent examples include proteins that are incorrectly cleaved by cell localization proteases (the presence of autoantibodies against the N-terminal sequence of p53 which is normally cleaved after the protein is targeted to the nucleus is one of the most specific biomarkers of lung cancer) or incorrectly glycosylated by cellular glycosylases (anti-MUC1-antibodies against a form of MUC1 that is incorrectly O-glycosylated is a biomarker for a variety of cancers). Even though p53 mutations are frequently observed in tumors, the specificity of the autoantibodies against this protein is almost always against the N-terminus of the protein—connecting the immunogenicity of p53 more to the ectopic expression of a protein that is normally short lived and located in the nucleus.

The detection of natural EGFR autoantibodies in serum of NSCLC patients has been described by Li et al.². Li et al.³and Chapman et al.⁴described the detection of natural autoantibodies to p53, HER2, NY-ESO-1, CAGE, MUC1 and GBU4-5. Further, WO2011073905⁵relates to tumor markers associated with the progression of a cancer disease from a less progressed stage to a more progressed stage. ²Li Yuan et al, Chinese Journal of Lung Cancer, 13(7), 2010, 727-730³Li Yuan et al, Chinese Journal of Lung Cancer, 12(10), 2009, 1999-6187⁴C J Chapman, A Murray, J E McElveen, U Sahin, U Luxemburger, Ö Türeci, R Wiewrodt, A C Barnes, J F Robertson, “Autoantibodies in lung cancer: possibilities for early detection and subsequent cure”, Thorax 2008; 63(3):228-233⁵WO2011073905

Unusual (mutated or expressed in abnormal quantities or locations) tumor proteins can invoke an antibody response. Tumor-induced autoantibodies have frequently been observed and their utility as diagnostic markers has been investigated (Albert and Darnell 2004⁶). While autoantibodies to tumor proteins can be found that have exquisite specificity, most of them lack the required sensitivity for a diagnostic test. ⁶Albert, M. L. and R. B. Darnell (2004). “Paraneoplastic neurological degenerations: Keys to tumor immunity.” Nat. Rev. Cancer 4(1): 36-44

Few reliable epidemiologic and genetic markers that predict erlotinib hydrochloride response are known in the art. In particular, EGFR mutations in exon 18-21 (intracellular kinase domain of the receptor) were described to be linked with better prognosis as well as with better response to TKI treatment (Paz-Ares, Soulieres et al. 2010⁷). The only predictive marker currently known (EGFR activating mutation) is difficult to diagnose as a biopsy of the tumor is needed. At present only about 50% of NSCLC patients are diagnosed with a biopsy (Reck, Hermes et al. 2011⁸). There is a definite need for simpler techniques to detect predictive markers of TKI efficacy. It is desirable to identify the responders at diagnosis in order to have as many patients as possible benefiting from erlotinib treatment as early as possible, while exploring other treatment options for patients not likely to respond. ⁷Paz-Ares, L., D. Soulieres, et al. (2010). “Clinical outcomes in non-small-cell lung cancer patients with EGFR mutations: pooled analysis.” J Cell Mol Med 14(1-2): 51-69⁸Reck, M., A. Hermes, et al. (2011). “Tissue sampling in lung cancer: A review in light of the MERIT experience.” Lung Cancer 74(1): 1-6

DETAILED DESCRIPTION OF THE INVENTION

Present invention solves that problem in that it provides a method of diagnosis of cancer in a human subject.

Present invention solves that problem in that it provides a method of diagnosis of non-small cell lung cancer in a human subject.

Present invention solves that problem in that it provides a method of diagnosis of non-small cell lung cancer in a human subject by providing antibodies against mutated EGFR sequences.

A patient identified by a method as described herein is a patient, in particular a NSCLC patient who will respond to the treatment with erlotinib or a pharmaceutically acceptable salt thereof, in particular erlotinib hydrochloride.

We surprisingly found that present autoantibodies possess the required sensitivity for a diagnostic test, especially autoantibodies against mutated EGFR sequences.

EGFR is normally bound to the cell membrane and not shed to the bloodstream. EGFR is a normal adult protein that is found in large quantities in some adult tissues. Immune tolerance is expected to be established against this protein and many of its variants. Almost all of the sequences belong to the cytoplasmic part of the molecule and are invisible to professional antigen presenting cells. The mutations affect only a small part of the EGFR molecule.

Unless defined otherwise, all terms used herein have the same meanings as commonly understood by a skilled artisan to which art this invention belongs.

The term “a level of said autoantibody representative for a human subject of a healthy population” refers to an estimate of the mean level of the autoantibody in serum of a population of patients who do not suffer from NSCLC.

The term “a level of said autoantibody representative for a NSCLC patient” refers to an estimate of the mean level of the autoantibody in serum of a population of patients who suffer from NSCLC.

The term “overall survival (OS)” refers to the length of time from diagnosis of disease during and after treatment the patient survives. As the skilled person will appreciate, a patient's overall survival is improved or enhanced, if the patient belongs to a subgroup of patients that has a statistically significant longer mean survival time as compared to another subgroup of patients.

The term “progression-free survival (PFS)” refers to the length of time from diagnosis of disease during and after treatment during which, according to the assessment of the treating physician or investigator, the patient's disease does not become worse, i.e., does not progress. As the skilled person will appreciate, a patient's progression-free survival is improved or enhanced if the patient belongs to a subgroup of patients that has a longer length of time during which the disease does not progress as compared to the average or mean progression free survival time of a control group of similarly situated patients.

The term “patient” refers to any single mammal for which treatment is desired. In particular, the “patient” is a human subject. More particularly, the patient is a human subject suffering from cancer, in particular NSCLC.

The term “autoantibody” is a type of protein manufactured by the immune system of a patient that is directed against one or more of the patient's own proteins.

The term “amino acid” denotes the group of naturally occurring carboxy a-amino acids comprising alanine (three letter code: ala, one letter code: A), arginine (arg, R), asparagine (asn, N), aspartic acid (asp, D), cysteine (cys, C), glutamine (gln, Q), glutamic acid (glu, E), glycine (gly, G), histidine (his, H), isoleucine (ile, I), leucine (leu, L), lysine (lys, K), methionine (met, M), phenylalanine (phe, F), proline (pro, P), serine (ser, S), threonine (thr, T), tryptophan (trp, W), tyrosine (tyr, Y), and valine (val, V).

As used herein, “therapy” or “treatment” (and grammatical variations thereof such as “treat” or “treating”) refers to clinical intervention in an attempt to alter the natural course of a disease in the individual being treated, and can be performed either for prophylaxis or during the course of clinical pathology. Desirable effects of treatment include, but are not limited to, preventing occurrence or recurrence of disease, alleviation of symptoms, diminishment of any direct or indirect pathological consequences of the disease, preventing metastasis, decreasing the rate of disease progression, amelioration or palliation of the disease state, and remission or improved prognosis.

The term “gene” as used herein comprises variants of the gene. The term “variant” relates to nucleic acid sequences which are substantially similar to the nucleic acid sequences given by the GenBank accession number. The term “substantially similar” is well understood by a person skilled in the art. In particular, a gene variant may be an allele which shows nucleotide exchanges compared to the nucleic acid sequence of the most prevalent allele in the human population. Preferably, such a substantially similar nucleic acid sequence has a sequence similarity to the most prevalent allele of at least 80%, preferably at least 85%, more preferably at least 90%, most preferably at least 95%. The term “variants” is also meant to relate to splice variants.

The term “mutation” refers to changes in a genomic sequence. These random sequences can be defined as sudden and spontaneous changes in the cell. Mutation can result in several different types of change in sequences; these can either have no effect, alter the product of a gene, or prevent the gene from functioning properly or completely. The term “somatic mutation” refers to a change in the genetic structure that is neither inherited nor passed to offspring.

The phrase “recommending a treatment” as used herein refers to using the information or data generated relating to the level or presence of a biomarker or an autoantibody in a sample of a patient to identify the patient as suitably treated or not suitably treated with a therapy. In some embodiment the therapy may comprise a drug. The information or data may be in any form, written, oral or electronic. In some embodiments, using the information or data generated includes communicating, presenting, reporting, storing, sending, transferring, supplying, transmitting, delivering, dispensing, or combinations thereof. In some embodiments, communicating, presenting, reporting, storing, sending, transferring, supplying, transmitting, delivering, dispensing, or combinations thereof are performed by a computing device, analyzer unit or combination thereof. In some further embodiments, communicating, presenting, reporting, storing, sending, transferring, supplying, transmitting, delivering, dispensing, or combinations thereof are performed by a laboratory or medical professional. In some embodiments, the information or data includes a comparison of the level of said biomarker or autoantibody to a reference level. In some embodiments, the information or data includes an indication that said biomarker or autoantibody is present or absent in the sample. In some embodiments, the information or data includes an indication that the patient is suitably treated or not suitably treated with a therapy comprising said drug. In some embodiments, the therapy is erlotinib.

The phrase “providing a diagnosis” as used herein refers to using the information or data generated relating to the level or presence of a biomarker or an autoantibody in a sample of a patient to diagnose a disease in the patent. The information or data may be in any form, written, oral or electronic. In some embodiments, using the information or data generated includes presenting, reporting, storing, sending, transferring, supplying, transmitting, delivering, dispensing, or combinations thereof. In some embodiments, presenting, reporting, storing, sending, transferring, supplying, transmitting, delivering, dispensing, or combinations thereof are performed by a computing device, analyzer unit or combination thereof. In some embodiments, presenting, reporting, storing, sending, transferring, supplying, transmitting, delivering, dispensing, or combinations thereof are performed by a laboratory or medical professional. In some embodiments, the information or data includes a comparison of the level of said biomarker or autoantibody to a reference level. In some embodiments, the information or data includes an indication that said biomarker or autoantibody is present or absent in the sample. In some embodiments, the information or data includes an indication that the patient is diagnosed with said disease. In some embodiments, said disease is non-small cell lung cancer.

During the TASK study, biopsy material had been collected and the tumor cells have been tested for the presence of the most frequent somatic mutations, i.e. a deletion at exon 19, and a point mutation at exon 21. During the TASK study serum samples had been collected at various time points (pre-dose, day 8, day 22 and progression) from all patients and were assessed for autoantibodies against EGFR.

In these patients, autoantigenic peptide sequences that predict development of rash, or prolonged progression free or overall survival inevitably include a set of sequences that are derived from the EGFR sequence starting at position 737 and extending through 756. These peptides include a number of sequence variants, but inevitably include sequences that have a deletion at position 746-750 or close nearby (Table 2).

This corresponds exactly to the position of the deletion in the exon 19 somatic mutation, known to be predictive for outstanding efficacy from treatment with TKI (Rosell et al. 2009⁹, Mok et al. 2009¹⁰). ⁹Rosell et al., N Engl J Med 2009; 361:958-967¹⁰Mok et al., N Engl J Med 2009; 361:947-957

The presence of a somatic EGFR mutation in exon 19 in tumor tissue leads to protein variant against that the immune system has not developed tolerance. The somatic mutation occurs only in the tumor, and therefore, if it induces an autoantibody which can be detected in the patient's serum it can be used to draw conclusions about the presence of an exon 19 mutation or exon 21 mutation in the NSCLC tissue, which is well known to predict increased progression free survival and superiority of tyrosine kinase monotherapy over chemotherapy (Heigener and Reck 2011¹¹). ¹¹Heigener, D. and M. Reck (2011). “Mutations in the epidermal growth factor receptor gene in non-small cell lung cancer: Impact on treatment beyond gefitinib and erlotinib.” Advances in Therapy 28(2): 126-133

The autoantibody can be detected using a standard blood sample from the patient without the need to obtain tumor cells with a biopsy. This is a large advantage over the current practice, as recovery rates of useful tumor samples even in clinical studies do not exceed 50% (Reck, Hermes et al. 2011¹²). ¹²Reck, M., A. Hermes, et al. (2011). “Tissue sampling in lung cancer: A review in light of the MERIT experience.” Lung Cancer 74(1): 1-6

Anti-EGFR autoantibodies can be detected in blood samples of NSCLC patients at higher concentrations than in healthy controls (FIG. 1). In particular, peptide sequences have been identified that yield consecutive regions of high immunogenicity with large differences between patient and healthy controls sera. Consecutive sequence stretches were identified, where ratios of individual peptide signals in more than 30% of the cancer patients to maximum value in controls was larger than 8 (Table 1).

TABLE 1

Consecutive EGFR sequences with high

autoantigenicity in NLSCL patients

Consensus sequence of

Sequence
autoantigenic

Protein
Region
peptides in the region

EGFR
323-336
VRKSKKSEGPSxKV

EGFR
546-564
PREFVENSECIQCHPECL

EGFR
574-591
RGPDNCIQCAHYIDGPHCVKTCP

EGFR
735-762
GEKVKIPVAIK[-S]PKANK

Del 1

EGFR
739-758
KIPVAIK[-HRK]PTSPK

Del 2

EGFR
793-806
MPFGCLLDYVREH

EGFR
867-883
KEYHAEGGKVPIKWM

EGFR
986-1002
RMHLPSPTDSNFYRA

EGFR
1081-1095
SIDDTFLPVPEYIN

EGFR
1148-1166
NSTFDSPAHWAQKGSHQI

The above sequences can be used for the early diagnosis of NSCLC.

Regression analysis has identified significant evidence that the presence of antibodies to the peptides influence both, progression free survival (PFS) and overall survival (OS) (FIG. 2). Although the number of samples is small in comparison to the number of peptides, many covariates need to be considered and none of the individual peptides reach sufficient statistical significance, we surprisingly found that when combining overlapping information from various independent statistical approaches, selection of a relevant peptide from the many candidates obtained after univariate analysis is possible. FIG. 3 illustrates the process that led to selection of the candidate sequences listed in Table 2. Sequences listed in Table 2 or any continuous subsequences thereof longer than 8 amino acids are candidate sequences.

TABLE 2

Antigenic sequences influencing PFS and OS of NSCLC patients

Consensus sequence of

Sequence
autoantigenic

Protein
Region
peptides in the region
Source

EGFR
737-756
KVKIPVAIKELREATSPKA
PFS ~ Peptide and

EGFR
737-756 Del
KVKIPVAIK------[SA]PKA
treatment in EGFR -

742-748

mutation positive

patients with rash

EGFR
763-776
A[YV]VMASVDNPHVCR
Consensus of

EGFR
703-717
LLRILKETE[FS]KKI
statistical

EGFR
825-838
MNYLEDR[RL]LVHRD
analyses for PFS

EGFR
296-309
KGNYVVTDHGSCVRA
Consensus of

EGFR
628-641
CTGPGLEGCPTNG
statistical

EGFR
681-727
RLLQEREL[VL]EPLTPSGEAPNQA[L
analyses for OS

PF]LR[IT]L[KM]ETE[FL]KK[IL]

[KF]VLG[SP]GAFGT

EGFR
761-780
DEAYVMASVDNPHVCRLLG

EGFR
830-843
YLEDRRLVHRDLA

TABLE 3

Examples for peptide sequences with high

predictive potential for prolonged

progression free survival in patients with

EGFR mutations that develop rash

KVKIPVAIKELREATSPKA
Annotation

KVKIPVAIK------APKA
737_V003

KVKIPVAIK---APTS
737_V004

KVKIPVAIKD------PKA
737_V007

KVKIPVAIKELKA
737_V015

KVKIPVAIKE------PKA
737_V019

KVKIPVAIKEQKA
737_V024

KVKIPVAIKESKA
737_V029

KVKIPVAIKEV-----PK
737_V037

KVKIPVAIK------IPKA
737_V039

KVKIPVAIK------SPKA
737_V054

KVKIPVAIK------TPKA
737_V057

--KIPVAIKE----ASPKA
739 V010

--KIPVAIKEF----SPKA
739_V013

--KIPVAIKE----NSPKA
739_V027

--KIPVAIK----VASPKA
739_V067

--KIPVAIK----VPSPKA
739_V070

EGFR peptide sequences selected from Seq. Id. No. 1-Seq. Id. No. 15 are consecutive sequences with high autoantigenicity in NLSCL patients.

EGFR peptide sequences selected from Seq. Id. No. 16-Seq. Id. No. 517 are useful for predicting the occurrence and grade of adverse events like rash to erlotinib treatment.

EGFR peptide sequences selected from Seq. Id. No. 518-Seq. Id. No. 602 are antigenic sequences influencing, in particular extending, progression free and overall survival of NSCLC patients, in particular mutated EGFR peptide sequences Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 556, Seq. Id. No. 557, Seq. Id. No. 558, Seq. Id. No. 559 and Seq. Id. No. 560, as well as EGFR peptide sequences Seq. Id. No. 519, Seq. Id. No. 520, Seq. Id. No. 521 and Seq. Id. No. 561.

EGFR peptide sequences selected from Seq. Id. No. 603-Seq. Id. No. 619 have high predictive potential for prolonged progression free survival in patients with EGFR mutations that develop rash.

Antibodies against these peptide sequences most likely influence PFS and OS if they are present in patients. Tests that detect the presence of these antibodies in patient sera could be used to guide treatment and stratify patients into treatment groups.

Present invention provides a method of diagnosis of non-small cell lung cancer in a human subject comprising:

measuring in a blood sample of the human subject a level of an autoantibody selected from the group of autoantibodies recognizing mutated human EGFR, wherein an increased level of said autoantibody selected from the group of autoantibodies recognizing mutated human EGFR in the blood sample of the human subject compared to a level of said autoantibody representative for a human subject of a healthy population is indicative for non-small cell lung cancer.

Present invention provides a method of diagnosis of non-small cell lung cancer in a human subject comprising:

a) measuring in a blood sample of the human subject a level of an autoantibody selected from the group of autoantibodies recognizing mutated human EGFR,

b) comparing the level of said autoantibody to a reference level, and

c) providing a diagnosis of non-small cell lung cancer when the level of said autoantibody is above the reference level.

Present invention provides a method of diagnosis of non-small cell lung cancer in a human subject comprising:

a) measuring in a blood sample of the human subject a level of an autoantibody selected from the group of autoantibodies recognizing mutated human EGFR,

b) comparing the level of said autoantibody to a reference level, and

c) recommending a treatment when the level of said autoantibody is above the reference level.

A certain embodiment of the present invention provides a method as described above, wherein said treatment is erlotinib.

A certain embodiment of present invention provides a method as described herein, wherein the level of an autoantibody recognizing mutated human EGFR is measured.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes a mutated EGFR peptide is selected from the group consisting of Seq. Id. No. 1, Seq. Id. No. 2, Seq. Id. No. 4, Seq. Id. No. 5, Seq. Id. No. 6, Seq. Id. No. 7, Seq. Id. No. 15, Seq. Id. No. 16, Seq. Id. No. 17, Seq. Id. No. 18, Seq. Id. No. 19, Seq. Id. No. 20, Seq. Id. No. 21, Seq. Id. No. 22, Seq. Id. No. 23, Seq. Id. No. 24, Seq. Id. No. 25, Seq. Id. No. 26, Seq. Id. No. 27, Seq. Id. No. 28, Seq. Id. No. 29, Seq. Id. No. 30, Seq. Id. No. 31, Seq. Id. No. 32, Seq. Id. No. 33, Seq. Id. No. 34, Seq. Id. No. 35, Seq. Id. No. 36, Seq. Id. No. 37, Seq. Id. No. 38, Seq. Id. No. 39, Seq. Id. No. 40, Seq. Id. No. 41, Seq. Id. No. 42, Seq. Id. No. 43, Seq. Id. No. 44, Seq. Id. No. 45, Seq. Id. No. 46, Seq. Id. No. 47, Seq. Id. No. 48, Seq. Id. No. 49, Seq. Id. No. 50, Seq. Id. No. 51, Seq. Id. No. 52, Seq. Id. No. 53, Seq. Id. No. 54, Seq. Id. No. 55, Seq. Id. No. 56, Seq. Id. 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A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the groups consisting of Seq. Id. No. 1, Seq. Id. No. 2, Seq. Id. No. 4, Seq. Id. No. 5, Seq. Id. No. 6, Seq. Id. No. 7 and Seq. Id. No. 15.

Id. No. 33, Seq. Id. No. 34, Seq. Id. No. 35, Seq. Id. No. 36, Seq. Id. No. 37, Seq. Id. No. 38, Seq. Id. No. 39, Seq. Id. No. 40, Seq. Id. No. 41, Seq. Id. No. 42, Seq. Id. No. 43, Seq. Id. No. 44, Seq. Id. No. 45, Seq. Id. No. 46, Seq. Id. No. 47, Seq. Id. No. 48, Seq. Id. No. 49, Seq. Id. No. 50, Seq. Id. No. 51, Seq. Id. No. 52, Seq. Id. No. 53, Seq. Id. No. 54, Seq. Id. No. 55, Seq. Id. No. 56, Seq. Id. No. 57, Seq. Id. No. 58, Seq. Id. No. 59, Seq. Id. No. 60, Seq. Id. No. 61, Seq. Id. No. 62, Seq. Id. No. 63, Seq. Id. No. 65, Seq. Id. No. 66, Seq. Id. No. 67, Seq. Id. No. 68, Seq. Id. No. 69, Seq. Id. No. 70, Seq. Id. No. 71, Seq. Id. No. 72, Seq. Id. No. 73, Seq. Id. No. 74, Seq. Id. No. 75, Seq. Id. No. 76, Seq. Id. No. 77, Seq. Id. No. 78, Seq. Id. No. 79, Seq. Id. No. 80, Seq. Id. No. 81, Seq. Id. No. 82, Seq. Id. No. 83, Seq. Id. No. 84, Seq. Id. No. 85, Seq. Id. No. 86, Seq. Id. No. 87, Seq. Id. No. 88, Seq. Id. No. 89, Seq. Id. No. 90, Seq. Id. No. 91, Seq. Id. 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No. 371, Seq. Id. No. 372, Seq. Id. No. 374, Seq. Id. No. 375, Seq. Id. No. 376, Seq. Id. No. 377, Seq. Id. No. 378, Seq. Id. No. 379, Seq. Id. No. 380, Seq. Id. No. 381, Seq. Id. No. 382, Seq. Id. No. 383, Seq. Id. No. 384, Seq. Id. No. 385, Seq. Id. No. 386, Seq. Id. No. 387, Seq. Id. No. 388, Seq. Id. No. 389, Seq. Id. No. 390, Seq. Id. No. 391, Seq. Id. No. 392, Seq. Id. No. 393, Seq. Id. No. 394, Seq. Id. No. 395, Seq. Id. No. 396, Seq. Id. No. 397, Seq. Id. No. 398, Seq. Id. No. 399, Seq. Id. No. 400, Seq. Id. No. 401, Seq. Id. No. 402, Seq. Id. No. 403, Seq. Id. No. 404, Seq. Id. No. 405, Seq. Id. No. 406, Seq. Id. No. 407, Seq. Id. No. 408, Seq. Id. No. 409, Seq. Id. No. 410, Seq. Id. No. 411, Seq. Id. No. 412, Seq. Id. No. 413, Seq. Id. No. 414, Seq. Id. No. 415, Seq. Id. No. 416, Seq. Id. No. 417, Seq. Id. No. 418, Seq. Id. No. 419, Seq. Id. No. 420, Seq. Id. No. 421, Seq. Id. No. 422, Seq. Id. No. 423, Seq. Id. No. 424, Seq. Id. No. 425, Seq. Id. No. 426, Seq. Id. No. 427, Seq. Id. No. 428, Seq. Id. No. 429, Seq. Id. No. 430, Seq. Id. No. 431, Seq. Id. No. 432, Seq. Id. No. 433, Seq. Id. No. 434, Seq. Id. No. 435, Seq. Id. No. 436, Seq. Id. No. 437, Seq. Id. No. 438, Seq. Id. No. 439, Seq. Id. No. 440, Seq. Id. No. 441, Seq. Id. No. 442, Seq. Id. No. 443, Seq. Id. No. 444, Seq. Id. No. 445, Seq. Id. No. 446, Seq. Id. No. 447, Seq. Id. No. 448, Seq. Id. No. 449, Seq. Id. No. 450, Seq. Id. No. 451, Seq. Id. No. 452, Seq. Id. No. 453, Seq. Id. No. 454, Seq. Id. No. 455, Seq. Id. No. 456, Seq. Id. No. 457, Seq. Id. No. 458, Seq. Id. No. 459, Seq. Id. No. 460, Seq. Id. No. 461, Seq. Id. No. 462, Seq. Id. No. 463, Seq. Id. No. 464, Seq. Id. No. 465, Seq. Id. No. 466, Seq. Id. No. 467, Seq. Id. No. 468, Seq. Id. No. 469, Seq. Id. No. 470, Seq. Id. No. 471, Seq. Id. No. 472, Seq. Id. No. 473, Seq. Id. No. 474, Seq. Id. No. 475, Seq. Id. No. 476, Seq. Id. No. 477, Seq. Id. No. 478, Seq. Id. No. 479, Seq. Id. No. 480, Seq. Id. No. 481, Seq. Id. No. 482, Seq. Id. No. 483, Seq. Id. No. 484, Seq. Id. No. 485, Seq. Id. No. 486, Seq. Id. No. 487, Seq. Id. No. 488, Seq. Id. No. 489, Seq. Id. No. 490, Seq. Id. No. 491, Seq. Id. No. 492, Seq. Id. No. 493, Seq. Id. No. 494, Seq. Id. No. 495, Seq. Id. No. 496, Seq. Id. No. 497, Seq. Id. No. 498, Seq. Id. No. 499, Seq. Id. No. 500, Seq. Id. No. 501, Seq. Id. No. 502, Seq. Id. No. 503, Seq. Id. No. 504, Seq. Id. No. 505, Seq. Id. No. 506, Seq. Id. No. 507, Seq. Id. No. 508, Seq. Id. No. 509, Seq. Id. No. 510, Seq. Id. No. 511, Seq. Id. No. 512, Seq. Id. No. 513, Seq. Id. No. 514, Seq. Id. No. 515, Seq. Id. No. 516 and Seq. Id. No. 517.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 518, Seq. Id. No. 522, Seq. Id. No. 523, Seq. Id. No. 524, Seq. Id. No. 526, Seq. Id. No. 527, Seq. Id. No. 528, Seq. Id. No. 529, Seq. Id. No. 530, Seq. Id. No. 531, Seq. Id. No. 532, Seq. Id. No. 533, Seq. Id. No. 534, Seq. Id. No. 535, Seq. Id. No. 536, Seq. Id. No. 537, Seq. Id. No. 538, Seq. Id. No. 539, Seq. Id. No. 540, Seq. Id. No. 541, Seq. Id. No. 542, Seq. Id. No. 543, Seq. Id. No. 544, Seq. Id. No. 545, Seq. Id. No. 546, Seq. Id. No. 547, Seq. Id. No. 548, Seq. Id. No. 549, Seq. Id. No. 550, Seq. Id. No. 551, Seq. Id. No. 552, Seq. Id. No. 553, Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 557, Seq. Id. No. 559, Seq. Id. No. 560, Seq. Id. No. 562, Seq. Id. No. 563, Seq. Id. No. 564, Seq. Id. No. 565, Seq. Id. No. 567, Seq. Id. No. 568, Seq. Id. No. 569, Seq. Id. No. 570, Seq. Id. No. 571, Seq. Id. No. 572, Seq. Id. No. 573, Seq. Id. No. 574, Seq. Id. No. 575, Seq. Id. No. 576, Seq. Id. No. 577, Seq. Id. No. 578, Seq. Id. No. 579, Seq. Id. No. 580, Seq. Id. No. 581, Seq. Id. No. 582, Seq. Id. No. 583, Seq. Id. No. 584, Seq. Id. No. 585, Seq. Id. No. 586, Seq. Id. No. 587, Seq. Id. No. 588, Seq. Id. No. 589, Seq. Id. No. 590, Seq. Id. No. 591, Seq. Id. No. 592, Seq. Id. No. 593, Seq. Id. No. 594, Seq. Id. No. 595, Seq. Id. No. 596, Seq. Id. No. 597, Seq. Id. No. 598, Seq. Id. No. 599 and Seq. Id. No. 601.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide that is selected from the group consisting of Seq. Id. No. 519, Seq. Id. No. 520, Seq. Id. No. 521, and Seq. Id. No. 561.

A certain embodiment of present invention provides a method as described herein, wherein the level of an autoantibody in the blood sample of the human subject is 5 times higher than the level of said autoantibody representative for a human subject of a healthy population.

A certain embodiment of present invention provides erlotinib or a pharmaceutically acceptable salt thereof, in particular erlotinib hydrochloride, for use in treating a NSCLC patient identified by a method as described herein comprising administering erlotinib or a pharmaceutically acceptable salt thereof, in particular erlotinib hydrochloride to the patient.

A certain embodiment of present invention provides the use of an autoantibody for predicting the response of a NSCLC patient to erlotinib or a pharmaceutically acceptable salt thereof, in particular erlotinib hydrochloride, treatment, which antibody was identified by a method as described herein.

A certain embodiment of present invention provides a kit for detecting in a blood sample of the human subject a level of one or more autoantibodies selected from the group of autoantibodies recognizing mutated human EGFR, wherein an increased level of said autoantibodies selected from the group of autoantibodies recognizing mutated human EGFR in the blood sample of the human subject compared to a level of said autoantibodies representative for a human subject of a healthy population is indicative for non-small cell lung cancer.

A certain embodiment of present invention provides a kit as described herein, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 16, Seq. Id. No. 17, Seq. Id. No. 18, Seq. Id. No. 19, Seq. Id. No. 20, Seq. Id. No. 21, Seq. Id. No. 22, Seq. Id. No. 23, Seq. Id. No. 24, Seq. Id. No. 25, Seq. Id. No. 26, Seq. Id. No. 27, Seq. Id. No. 28, Seq. Id. No. 29, Seq. Id. No. 30, Seq. Id. No. 31, Seq. Id. No. 32, Seq. Id. No. 33, Seq. Id. No. 34, Seq. Id. No. 35, Seq. Id. No. 36, Seq. Id. No. 37, Seq. Id. No. 38, Seq. Id. No. 39, Seq. Id. No. 40, Seq. Id. No. 41, Seq. Id. No. 42, Seq. Id. No. 43, Seq. Id. No. 44, Seq. Id. No. 45, Seq. Id. No. 46, Seq. Id. No. 47, Seq. Id. No. 48, Seq. Id. No. 49, Seq. Id. No. 50, Seq. Id. No. 51, Seq. Id. No. 52, Seq. Id. No. 53, Seq. Id. No. 54, Seq. Id. No. 55, Seq. Id. No. 56, Seq. Id. No. 57, Seq. Id. No. 58, Seq. Id. No. 59, Seq. Id. No. 60, Seq. Id. No. 61, Seq. Id. No. 62, Seq. Id. No. 63, Seq. Id. No. 65, Seq. Id. No. 66, Seq. Id. No. 67, Seq. Id. No. 68, Seq. Id. No. 69, Seq. Id. No. 70, Seq. Id. No. 71, Seq. Id. No. 72, Seq. Id. No. 73, Seq. Id. No. 74, Seq. Id. No. 75, Seq. Id. No. 76, Seq. Id. No. 77, Seq. Id. No. 78, Seq. Id. No. 79, Seq. Id. No. 80, Seq. Id. No. 81, Seq. Id. No. 82, Seq. Id. No. 83, Seq. Id. No. 84, Seq. Id. No. 85, Seq. Id. No. 86, Seq. Id. No. 87, Seq. Id. No. 88, Seq. Id. No. 89, Seq. Id. No. 90, Seq. Id. No. 91, Seq. Id. No. 92, Seq. Id. No. 93, Seq. Id. No. 94, Seq. Id. No. 95, Seq. Id. No. 96, Seq. Id. No. 97, Seq. Id. No. 98, Seq. Id. No. 99, Seq. Id. No. 100, Seq. Id. No. 101, Seq. Id. No. 103, Seq. Id. No. 104, Seq. Id. No. 105, Seq. Id. No. 106, Seq. Id. No. 107, Seq. Id. No. 108, Seq. Id. No. 109, Seq. Id. No. 110, Seq. Id. No. 111, Seq. Id. No. 112, Seq. Id. No. 113, Seq. Id. No. 114, Seq. Id. No. 115, Seq. Id. No. 116, Seq. Id. No. 117, Seq. Id. No. 118, Seq. Id. No. 119, Seq. Id. No. 120, Seq. Id. No. 121, Seq. Id. No. 122, Seq. Id. No. 123, Seq. Id. No. 124, Seq. Id. No. 125, Seq. Id. No. 126, Seq. Id. No. 127, Seq. Id. No. 128, Seq. Id. No. 129, Seq. Id. No. 130, Seq. Id. No. 131, Seq. Id. No. 132, Seq. Id. No. 133, Seq. Id. No. 134, Seq. Id. No. 135, Seq. Id. No. 136, Seq. Id. No. 137, Seq. Id. No. 138, Seq. Id. No. 139, Seq. Id. No. 140, Seq. Id. No. 141, Seq. Id. No. 142, Seq. Id. No. 143, Seq. Id. No. 144, Seq. Id. No. 145, Seq. Id. No. 146, Seq. Id. No. 147, Seq. Id. No. 148, Seq. Id. No. 149, Seq. Id. No. 150, Seq. Id. No. 151, Seq. Id. No. 152, Seq. Id. No. 153, Seq. Id. No. 154, Seq. Id. No. 155, Seq. Id. No. 156, Seq. Id. No. 157, Seq. Id. No. 158, Seq. Id. No. 159, Seq. Id. No. 160, Seq. Id. No. 161, Seq. Id. No. 162, Seq. Id. No. 163, Seq. Id. No. 164, Seq. Id. No. 165, Seq. Id. No. 166, Seq. Id. No. 167, Seq. Id. No. 168, Seq. Id. No. 169, Seq. Id. No. 170, Seq. Id. No. 171, Seq. Id. No. 172, Seq. Id. No. 173, Seq. Id. No. 174, Seq. Id. No. 175, Seq. Id. No. 176, Seq. Id. No. 177, Seq. Id. No. 178, Seq. Id. No. 179, Seq. Id. No. 180, Seq. Id. No. 181, Seq. Id. No. 182, Seq. Id. No. 183, Seq. Id. No. 184, Seq. Id. No. 185, Seq. Id. No. 186, Seq. Id. No. 187, Seq. Id. No. 188, Seq. Id. No. 189, Seq. Id. No. 190, Seq. Id. No. 191, Seq. Id. No. 192, Seq. Id. No. 193, Seq. Id. No. 194, Seq. Id. No. 195, Seq. Id. No. 196, Seq. Id. No. 197, Seq. Id. No. 198, Seq. Id. No. 199, Seq. Id. No. 200, Seq. Id. No. 201, Seq. Id. No. 202, Seq. Id. No. 203, Seq. Id. No. 204, Seq. Id. No. 205, Seq. Id. No. 206, Seq. Id. No. 207, Seq. Id. No. 208, Seq. Id. No. 209, Seq. Id. No. 210, Seq. Id. No. 211, Seq. Id. No. 212, Seq. Id. No. 213, Seq. Id. No. 214, Seq. Id. No. 215, Seq. Id. No. 216, Seq. Id. No. 217, Seq. Id. No. 218, Seq. Id. No. 219, Seq. Id. No. 220, Seq. Id. No. 221, Seq. Id. No. 222, Seq. Id. No. 223, Seq. Id. No. 224, Seq. Id. No. 225, Seq. Id. No. 226, Seq. Id. No. 227, Seq. Id. No. 228, Seq. Id. No. 229, Seq. Id. No. 230, Seq. Id. No. 231, Seq. Id. No. 232, Seq. Id. No. 233, Seq. Id. No. 234, Seq. Id. No. 235, Seq. Id. No. 236, Seq. Id. No. 237, Seq. Id. No. 238, Seq. Id. No. 239, Seq. Id. No. 240, Seq. Id. No. 241, Seq. Id. No. 242, Seq. Id. No. 243, Seq. Id. No. 244, Seq. Id. No. 245, Seq. Id. No. 246, Seq. Id. No. 247, Seq. Id. No. 248, Seq. Id. No. 249, Seq. Id. No. 250, Seq. Id. No. 251, Seq. Id. No. 252, Seq. Id. No. 253, Seq. Id. No. 254, Seq. Id. No. 255, Seq. Id. No. 256, Seq. Id. No. 257, Seq. Id. No. 258, Seq. Id. No. 259, Seq. Id. No. 260, Seq. Id. No. 261, Seq. Id. No. 262, Seq. Id. No. 263, Seq. Id. No. 264, Seq. Id. No. 265, Seq. Id. No. 266, Seq. Id. No. 267, Seq. Id. No. 268, Seq. Id. No. 269, Seq. Id. No. 270, Seq. Id. No. 271, Seq. Id. No. 272, Seq. Id. No. 273, Seq. Id. No. 274, Seq. Id. No. 275, Seq. Id. No. 276, Seq. Id. No. 277, Seq. Id. No. 278, Seq. Id. No. 279, Seq. Id. No. 280, Seq. Id. No. 281, Seq. Id. No. 282, Seq. Id. No. 283, Seq. Id. No. 284, Seq. Id. No. 285, Seq. Id. No. 286, Seq. Id. No. 287, Seq. Id. No. 288, Seq. Id. No. 289, Seq. Id. No. 290, Seq. Id. No. 291, Seq. Id. No. 292, Seq. Id. No. 293, Seq. Id. No. 294, Seq. Id. No. 295, Seq. Id. No. 296, Seq. Id. No. 297, Seq. Id. No. 298, Seq. Id. No. 299, Seq. Id. No. 300, Seq. Id. No. 301, Seq. Id. No. 302, Seq. Id. No. 303, Seq. Id. No. 304, Seq. Id. No. 305, Seq. Id. No. 306, Seq. Id. No. 307, Seq. Id. No. 308, Seq. Id. No. 310, Seq. Id. No. 311, Seq. Id. No. 312, Seq. Id. No. 313, Seq. Id. No. 314, Seq. Id. No. 315, Seq. Id. No. 316, Seq. Id. No. 317, Seq. Id. No. 318, Seq. Id. No. 319, Seq. Id. No. 320, Seq. Id. No. 321, Seq. Id. No. 322, Seq. Id. No. 323, Seq. Id. No. 324, Seq. Id. No. 325, Seq. Id. No. 326, Seq. Id. No. 327, Seq. Id. No. 328, Seq. Id. No. 329, Seq. Id. No. 330, Seq. Id. No. 331, Seq. Id. No. 332, Seq. Id. No. 333, Seq. Id. No. 334, Seq. Id. No. 335, Seq. Id. No. 336, Seq. Id. No. 337, Seq. Id. No. 338, Seq. Id. No. 339, Seq. Id. No. 340, Seq. Id. No. 341, Seq. Id. No. 342, Seq. Id. No. 343, Seq. Id. No. 344, Seq. Id. No. 345, Seq. Id. No. 346, Seq. Id. No. 347, Seq. Id. No. 348, Seq. Id. No. 349, Seq. Id. No. 350, Seq. Id. No. 351, Seq. Id. No. 352, Seq. Id. No. 353, Seq. Id. No. 354, Seq. Id. No. 355, Seq. Id. No. 356, Seq. Id. No. 357, Seq. Id. No. 358, Seq. Id. No. 359, Seq. Id. No. 360, Seq. Id. No. 361, Seq. Id. No. 362, Seq. Id. No. 363, Seq. Id. No. 364, Seq. Id. No. 365, Seq. Id. No. 366, Seq. Id. No. 367, Seq. Id. No. 368, Seq. Id. No. 369, Seq. Id. No. 371, Seq. Id. No. 372, Seq. Id. No. 374, Seq. Id. No. 375, Seq. Id. No. 376, Seq. Id. No. 377, Seq. Id. No. 378, Seq. Id. No. 379, Seq. Id. No. 380, Seq. Id. No. 381, Seq. Id. No. 382, Seq. Id. No. 383, Seq. Id. No. 384, Seq. Id. No. 385, Seq. Id. No. 386, Seq. Id. No. 387, Seq. Id. No. 388, Seq. Id. No. 389, Seq. Id. No. 390, Seq. Id. No. 391, Seq. Id. No. 392, Seq. Id. No. 393, Seq. Id. No. 394, Seq. Id. No. 395, Seq. Id. No. 396, Seq. Id. No. 397, Seq. Id. No. 398, Seq. Id. No. 399, Seq. Id. No. 400, Seq. Id. No. 401, Seq. Id. No. 402, Seq. Id. No. 403, Seq. Id. No. 404, Seq. Id. No. 405, Seq. Id. No. 406, Seq. Id. No. 407, Seq. Id. No. 408, Seq. Id. No. 409, Seq. Id. No. 410, Seq. Id. No. 411, Seq. Id. No. 412, Seq. Id. No. 413, Seq. Id. No. 414, Seq. Id. No. 415, Seq. Id. No. 416, Seq. Id. No. 417, Seq. Id. No. 418, Seq. Id. No. 419, Seq. Id. No. 420, Seq. Id. No. 421, Seq. Id. No. 422, Seq. Id. No. 423, Seq. Id. No. 424, Seq. Id. No. 425, Seq. Id. No. 426, Seq. Id. No. 427, Seq. Id. No. 428, Seq. Id. No. 429, Seq. Id. No. 430, Seq. Id. No. 431, Seq. Id. No. 432, Seq. Id. No. 433, Seq. Id. No. 434, Seq. Id. No. 435, Seq. Id. No. 436, Seq. Id. No. 437, Seq. Id. No. 438, Seq. Id. No. 439, Seq. Id. No. 440, Seq. Id. No. 441, Seq. Id. No. 442, Seq. Id. No. 443, Seq. Id. No. 444, Seq. Id. No. 445, Seq. Id. No. 446, Seq. Id. No. 447, Seq. Id. No. 448, Seq. Id. No. 449, Seq. Id. No. 450, Seq. Id. No. 451, Seq. Id. No. 452, Seq. Id. No. 453, Seq. Id. No. 454, Seq. Id. No. 455, Seq. Id. No. 456, Seq. Id. No. 457, Seq. Id. No. 458, Seq. Id. No. 459, Seq. Id. No. 460, Seq. Id. No. 461, Seq. Id. No. 462, Seq. Id. No. 463, Seq. Id. No. 464, Seq. Id. No. 465, Seq. Id. No. 466, Seq. Id. No. 467, Seq. Id. No. 468, Seq. Id. No. 469, Seq. Id. No. 470, Seq. Id. No. 471, Seq. Id. No. 472, Seq. Id. No. 473, Seq. Id. No. 474, Seq. Id. No. 475, Seq. Id. No. 476, Seq. Id. No. 477, Seq. Id. No. 478, Seq. Id. No. 479, Seq. Id. No. 480, Seq. Id. No. 481, Seq. Id. No. 482, Seq. Id. No. 483, Seq. Id. No. 484, Seq. Id. No. 485, Seq. Id. No. 486, Seq. Id. No. 487, Seq. Id. No. 488, Seq. Id. No. 489, Seq. Id. No. 490, Seq. Id. No. 491, Seq. Id. No. 492, Seq. Id. No. 493, Seq. Id. No. 494, Seq. Id. No. 495, Seq. Id. No. 496, Seq. Id. No. 497, Seq. Id. No. 498, Seq. Id. No. 499, Seq. Id. No. 500, Seq. Id. No. 501, Seq. Id. No. 502, Seq. Id. No. 503, Seq. Id. No. 504, Seq. Id. No. 505, Seq. Id. No. 506, Seq. Id. No. 507, Seq. Id. No. 508, Seq. Id. No. 509, Seq. Id. No. 510, Seq. Id. No. 511, Seq. Id. No. 512, Seq. Id. No. 513, Seq. Id. No. 514, Seq. Id. No. 515, Seq. Id. No. 516 and Seq. Id. No. 517.

A certain embodiment of present invention provides a kit as described herein, wherein the autoantibody recognizes an EGFR peptide that is selected from the group consisting of Seq. Id. No. 519, Seq. Id. No. 520, Seq. Id. No. 521, and Seq. Id. No. 561.

A certain embodiment of present invention provides a method of diagnosis of non-small cell lung cancer in a human subject comprising:

measuring in a blood sample of the human subject a level of an autoantibody selected from the group of autoantibodies recognizing human EGFR, wherein an increased level of said autoantibody selected from the group of autoantibodies recognizing human EGFR in the blood sample of the human subject compared to a level of said autoantibody representative for a human subject of a healthy population is indicative for non-small cell lung cancer, in particular wherein the level of an autoantibody recognizing human EGFR is measured.

Present invention provides a method of diagnosis of non-small cell lung cancer in a human subject comprising:

a) measuring in a blood sample of the human subject a level of an autoantibody selected from the group of autoantibodies recognizing human EGFR,

b) comparing the level of said autoantibody to a reference level, and

c) providing a diagnosis of non-small cell lung cancer when the level of said autoantibody is above the reference level.

Present invention provides a method of diagnosis of non-small cell lung cancer in a human subject comprising:

a) measuring in a blood sample of the human subject a level of an autoantibody selected from the group of autoantibodies recognizing mutated human EGFR,

b) comparing the level of said autoantibody to a reference level, and

c) recommending a treatment when the level of said autoantibody is above the reference level.

A certain embodiment of the present invention provides a method as described above, wherein said treatment is erlotinib.

A certain embodiment of present invention provides a method as described above, wherein the autoantibody recognizes an EGFR peptide is selected from the group consisting of Seq. Id. No. 1, Seq. Id. No. 2, Seq. Id. No. 3, Seq. Id. No. 4, Seq. Id. No. 5, Seq. Id. No. 6, Seq. Id. No. 7, Seq. Id. No. 8, Seq. Id. No. 9, Seq. Id. No. 10, Seq. Id. No. 11, Seq. Id. No. 12, Seq. Id. No. 13, Seq. Id. No. 14, Seq. Id. No. 15, Seq. Id. No. 16, Seq. Id. No. 17, Seq. Id. No. 18, Seq. Id. No. 19, Seq. Id. No. 20, Seq. Id. No. 21, Seq. Id. No. 22, Seq. Id. No. 23, Seq. Id. No. 24, Seq. Id. No. 25, Seq. Id. No. 26, Seq. Id. No. 27, Seq. Id. No. 28, Seq. Id. No. 29, Seq. Id. No. 30, Seq. Id. No. 31, Seq. Id. No. 32, Seq. Id. No. 33, Seq. Id. No. 34, Seq. Id. No. 35, Seq. Id. No. 36, Seq. Id. No. 37, Seq. Id. No. 38, Seq. Id. No. 39, Seq. Id. No. 40, Seq. Id. No. 41, Seq. Id. No. 42, Seq. Id. No. 43, Seq. Id. No. 44, Seq. Id. No. 45, Seq. Id. No. 46, Seq. Id. No. 47, Seq. Id. No. 48, Seq. Id. No. 49, Seq. Id. No. 50, Seq. Id. No. 51, Seq. Id. No. 52, Seq. Id. No. 53, Seq. Id. No. 54, Seq. Id. No. 55, Seq. Id. No. 56, Seq. Id. No. 57, Seq. Id. No. 58, Seq. Id. No. 59, Seq. Id. No. 60, Seq. Id. No. 61, Seq. Id. No. 62, Seq. Id. No. 63, Seq. Id. No. 64, Seq. Id. No. 65, Seq. Id. No. 66, Seq. Id. No. 67, Seq. Id. No. 68, Seq. Id. No. 69, Seq. Id. No. 70, Seq. Id. No. 71, Seq. Id. No. 72, Seq. Id. No. 73, Seq. Id. No. 74, Seq. Id. No. 75, Seq. Id. No. 76, Seq.

Id. No. 77, Seq. Id. No. 78, Seq. Id. No. 79, Seq. Id. No. 80, Seq. Id. No. 81, Seq. Id. No. 82, Seq. Id. No. 83, Seq. Id. No. 84, Seq. Id. No. 85, Seq. Id. No. 86, Seq. Id. No. 87, Seq. Id. No. 88, Seq. Id. No. 89, Seq. Id. No. 90, Seq. Id. No. 91, Seq. Id. No. 92, Seq. Id. No. 93, Seq. Id. No. 94, Seq. Id. No. 95, Seq. Id. No. 96, Seq. Id. No. 97, Seq. Id. No. 98, Seq. Id. No. 99, Seq. Id. No. 100, Seq. Id. No. 101, Seq. Id. No. 102, Seq. Id. No. 103, Seq. Id. No. 104, Seq. Id. No. 105, Seq. Id. No. 106, Seq. Id. No. 107, Seq. Id. No. 108, Seq. Id. No. 109, Seq. Id. No. 110, Seq. Id. No. 111, Seq. Id. No. 112, Seq. Id. No. 113, Seq. Id. No. 114, Seq. Id. No. 115, Seq. Id. No. 116, Seq. Id. No. 117, Seq. Id. No. 118, Seq. Id. No. 119, Seq. Id. No. 120, Seq. Id. No. 121, Seq. Id. No. 122, Seq. Id. No. 123, Seq. Id. No. 124, Seq. Id. No. 125, Seq. Id. No. 126, Seq. Id. No. 127, Seq. Id. No. 128, Seq. Id. No. 129, Seq. Id. No. 130, Seq. Id. No. 131, Seq. Id. No. 132, Seq. Id. No. 133, Seq. Id. No. 134, Seq. Id. No. 135, Seq. Id. No. 136, Seq. Id. No. 137, Seq. Id. No. 138, Seq. Id. No. 139, Seq. Id. No. 140, Seq. Id. No. 141, Seq. Id. No. 142, Seq. Id. No. 143, Seq. Id. No. 144, Seq. Id. No. 145, Seq. Id. No. 146, Seq. Id. No. 147, Seq. Id. No. 148, Seq. Id. No. 149, Seq. Id. No. 150, Seq. Id. No. 151, Seq. Id. No. 152, Seq. Id. No. 153, Seq. Id. No. 154, Seq. Id. No. 155, Seq. Id. No. 156, Seq. Id. No. 157, Seq. Id. No. 158, Seq. Id. No. 159, Seq. Id. No. 160, Seq. Id. No. 161, Seq. Id. No. 162, Seq. Id. No. 163, Seq. Id. No. 164, Seq. Id. No. 165, Seq. Id. No. 166, Seq. Id. No. 167, Seq. Id. No. 168, Seq. Id. No. 169, Seq. Id. No. 170, Seq. Id. No. 171, Seq. Id. No. 172, Seq. Id. No. 173, Seq. Id. No. 174, Seq. Id. No. 175, Seq. Id. No. 176, Seq. Id. No. 177, Seq. Id. No. 178, Seq. Id. No. 179, Seq. Id. No. 180, Seq. Id. No. 181, Seq. Id. No. 182, Seq. Id. No. 183, Seq. Id. No. 184, Seq. Id. No. 185, Seq. Id. No. 186, Seq. Id. No. 187, Seq. Id. No. 188, Seq. Id. No. 189, Seq. Id. No. 190, Seq. Id. No. 191, Seq. Id. No. 192, Seq. Id. No. 193, Seq. Id. No. 194, Seq. Id. No. 195, Seq. Id. No. 196, Seq. Id. No. 197, Seq. Id. No. 198, Seq. Id. No. 199, Seq. Id. No. 200, Seq. Id. No. 201, Seq. Id. No. 202, Seq. Id. No. 203, Seq. Id. No. 204, Seq. Id. No. 205, Seq. Id. No. 206, Seq. Id. No. 207, Seq. Id. No. 208, Seq. Id. No. 209, Seq. Id. No. 210, Seq. Id. No. 211, Seq. Id. No. 212, Seq. Id. No. 213, Seq. Id. No. 214, Seq. Id. No. 215, Seq. Id. No. 216, Seq. Id. No. 217, Seq. Id. No. 218, Seq. Id. No. 219, Seq. Id. No. 220, Seq. Id. No. 221, Seq. Id. No. 222, Seq. Id. No. 223, Seq. Id. No. 224, Seq. Id. No. 225, Seq. Id. No. 226, Seq. Id. No. 227, Seq. Id. No. 228, Seq. Id. No. 229, Seq. Id. No. 230, Seq. Id. No. 231, Seq. Id. No. 232, Seq. Id. No. 233, Seq. Id. No. 234, Seq. Id. No. 235, Seq. Id. No. 236, Seq. Id. No. 237, Seq. Id. No. 238, Seq. Id. No. 239, Seq. Id. No. 240, Seq. Id. No. 241, Seq. Id. No. 242, Seq. Id. No. 243, Seq. Id. No. 244, Seq. Id. No. 245, Seq. Id. No. 246, Seq. Id. No. 247, Seq. Id. No. 248, Seq. Id. No. 249, Seq. Id. No. 250, Seq. Id. No. 251, Seq. Id. No. 252, Seq. Id. No. 253, Seq. Id. No. 254, Seq. Id. No. 255, Seq. Id. No. 256, Seq. Id. No. 257, Seq. Id. No. 258, Seq. Id. No. 259, Seq. Id. No. 260, Seq. Id. No. 261, Seq. Id. No. 262, Seq. Id. No. 263, Seq. Id. No. 264, Seq. Id. No. 265, Seq. Id. No. 266, Seq. Id. No. 267, Seq. Id. No. 268, Seq. Id. No. 269, Seq. Id. No. 270, Seq. Id. No. 271, Seq. Id. No. 272, Seq. Id. No. 273, Seq. Id. No. 274, Seq. Id. No. 275, Seq. Id. No. 276, Seq. Id. No. 277, Seq. Id. No. 278, Seq. Id. No. 279, Seq. Id. No. 280, Seq. Id. No. 281, Seq. Id. No. 282, Seq. Id. No. 283, Seq. Id. No. 284, Seq. Id. No. 285, Seq. Id. No. 286, Seq. Id. No. 287, Seq. Id. No. 288, Seq. Id. No. 289, Seq. Id. No. 290, Seq. Id. No. 291, Seq. Id. No. 292, Seq. Id. No. 293, Seq. Id. No. 294, Seq. Id. No. 295, Seq. Id. No. 296, Seq. Id. No. 297, Seq. Id. No. 298, Seq. Id. No. 299, Seq. Id. No. 300, Seq. Id. No. 301, Seq. Id. No. 302, Seq. Id. No. 303, Seq. Id. No. 304, Seq. Id. No. 305, Seq. Id. No. 306, Seq. Id. No. 307, Seq. Id. No. 308, Seq. Id. No. 309, Seq. Id. No. 310, Seq. Id. No. 311, Seq. Id. No. 312, Seq. Id. No. 313, Seq. Id. No. 314, Seq. Id. No. 315, Seq. Id. No. 316, Seq. Id. No. 317, Seq. Id. No. 318, Seq. Id. No. 319, Seq. Id. No. 320, Seq. Id. No. 321, Seq. Id. No. 322, Seq. Id. No. 323, Seq. Id. No. 324, Seq. Id. No. 325, Seq. Id. No. 326, Seq. Id. No. 327, Seq. Id. No. 328, Seq. Id. No. 329, Seq. Id. No. 330, Seq. Id. No. 331, Seq. Id. No. 332, Seq. Id. No. 333, Seq. Id. No. 334, Seq. Id. No. 335, Seq. Id. No. 336, Seq. Id. No. 337, Seq. Id. No. 338, Seq. Id. No. 339, Seq. Id. No. 340, Seq. Id. No. 341, Seq. Id. No. 342, Seq. Id. No. 343, Seq. Id. No. 344, Seq. Id. No. 345, Seq. Id. No. 346, Seq. Id. No. 347, Seq. Id. No. 348, Seq. Id. No. 349, Seq. Id. No. 350, Seq. Id. No. 351, Seq. Id. No. 352, Seq. Id. 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No. 463, Seq. Id. No. 464, Seq. Id. No. 465, Seq. Id. No. 466, Seq. Id. No. 467, Seq. Id. No. 468, Seq. Id. No. 469, Seq. Id. No. 470, Seq. Id. No. 471, Seq. Id. No. 472, Seq. Id. No. 473, Seq. Id. No. 474, Seq. Id. No. 475, Seq. Id. No. 476, Seq. Id. No. 477, Seq. Id. No. 478, Seq. Id. No. 479, Seq. Id. No. 480, Seq. Id. No. 481, Seq. Id. No. 482, Seq. Id. No. 483, Seq. Id. No. 484, Seq. Id. No. 485, Seq. Id. No. 486, Seq. Id. No. 487, Seq. Id. No. 488, Seq. Id. No. 489, Seq. Id. No. 490, Seq. Id. No. 491, Seq. Id. No. 492, Seq. Id. No. 493, Seq. Id. No. 494, Seq. Id. No. 495, Seq. Id. No. 496, Seq. Id. No. 497, Seq. Id. No. 498, Seq. Id. No. 499, Seq. Id. No. 500, Seq. Id. No. 501, Seq. Id. No. 502, Seq. Id. No. 503, Seq. Id. No. 504, Seq. Id. No. 505, Seq. Id. No. 506, Seq. Id. No. 507, Seq. Id. No. 508, Seq. Id. No. 509, Seq. Id. No. 510, Seq. Id. No. 511, Seq. Id. No. 512, Seq. Id. No. 513, Seq. Id. No. 514, Seq. Id. No. 515, Seq. Id. No. 516, Seq. Id. No. 517, Seq. Id. No. 518, Seq. Id. No. 519, Seq. Id. No. 520, Seq. Id. No. 521, Seq. Id. No. 522, Seq. Id. No. 523, Seq. Id. No. 524, Seq. Id. No. 525, Seq. Id. No. 526, Seq. Id. No. 527, Seq. Id. No. 528, Seq. Id. No. 529, Seq. Id. No. 530, Seq. Id. No. 531, Seq. Id. No. 532, Seq. Id. No. 533, Seq. Id. No. 534, Seq. Id. No. 535, Seq. Id. No. 536, Seq. Id. No. 537, Seq. Id. No. 538, Seq. Id. No. 539, Seq. Id. No. 540, Seq. Id. No. 541, Seq. Id. No. 542, Seq. Id. No. 543, Seq. Id. No. 544, Seq. Id. No. 545, Seq. Id. No. 546, Seq. Id. No. 547, Seq. Id. No. 548, Seq. Id. No. 549, Seq. Id. No. 550, Seq. Id. No. 551, Seq. Id. No. 552, Seq. Id. No. 553, Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 556, Seq. Id. No. 557, Seq. Id. No. 558, Seq. Id. No. 559, Seq. Id. No. 560, Seq. Id. No. 561, Seq. Id. No. 562, Seq. Id. No. 563, Seq. Id. No. 564, Seq. Id. No. 565, Seq. Id. No. 566, Seq. Id. No. 567, Seq. Id. No. 568, Seq. Id. No. 569, Seq. Id. No. 570, Seq. Id. No. 571, Seq. Id. No. 572, Seq. Id. No. 573, Seq. Id. No. 574, Seq. Id. No. 575, Seq. Id. No. 576, Seq. Id. No. 577, Seq. Id. No. 578, Seq. Id. No. 579, Seq. Id. No. 580, Seq. Id. No. 581, Seq. Id. No. 582, Seq. Id. No. 583, Seq. Id. No. 584, Seq. Id. No. 585, Seq. Id. No. 586, Seq. Id. No. 587, Seq. Id. No. 588, Seq. Id. No. 589, Seq. Id. No. 590, Seq. Id. No. 591, Seq. Id. No. 592, Seq. Id. No. 593, Seq. Id. No. 594, Seq. Id. No. 595, Seq. Id. No. 596, Seq. Id. No. 597, Seq. Id. No. 598, Seq. Id. No. 599, Seq. Id. No. 600, Seq. Id. No. 601, Seq. Id. No. 602, Seq. Id. No. 603, Seq. Id. No. 604, Seq. Id. No. 605, Seq. Id. No. 606, Seq. Id. No. 607, Seq. Id. No. 608, Seq. Id. No. 609, Seq. Id. No. 610, Seq. Id. No. 611, Seq. Id. No. 612, Seq. Id. No. 613, Seq. Id. No. 614, Seq. Id. No. 615, Seq. Id. No. 616, Seq. Id. No. 617, Seq. Id. No. 618, and Seq. Id. No. 619.

A certain embodiment of present invention provides a method as described above, wherein the autoantibody recognizes an EGFR peptide that is selected from the group consisting of Seq. Id. No. 3, Seq. Id. No. 8, Seq. Id. No. 9, Seq. Id. No. 10, Seq. Id. No. 11, Seq. Id. No. 12, Seq. Id. No. 13, Seq. Id. No. 14, Seq. Id. No. 64, Seq. Id. No. 102, Seq. Id. No. 309, Seq. Id. No. 370, Seq. Id. No. 373, Seq. Id. No. 519, Seq. Id. No. 520, Seq. Id. No. 521, Seq. Id. No. 525, Seq. Id. No. 556, Seq. Id. No. 558, Seq. Id. No. 561, Seq. Id. No. 566, Seq. Id. No. 600, Seq. Id. No. 602 and Seq. Id. No. 603.

A certain embodiment of present invention provides a kit for detecting in a blood sample of the human subject a level of one or more autoantibodies selected from the group of autoantibodies recognizing human EGFR, wherein an increased level of said autoantibodies selected from the group of autoantibodies recognizing human EGFR in the blood sample of the human subject compared to a level of said autoantibodies representative for a human subject of a healthy population is indicative for non-small cell lung cancer.

A certain embodiment of present invention provides a kit as described above, wherein the autoantibody recognizes an EGFR peptide that is selected from the group consisting of Seq. Id. No. 3, Seq. Id. No. 8, Seq. Id. No. 9, Seq. Id. No. 10, Seq. Id. No. 11, Seq. Id. No. 12, Seq. Id. No. 13, Seq. Id. No. 14, Seq. Id. No. 64, Seq. Id. No. 102, Seq. Id. No. 309, Seq. Id. No. 370, Seq. Id. No. 373, Seq. Id. No. 519, Seq. Id. No. 520, Seq. Id. No. 521, Seq. Id. No. 525, Seq. Id. No. 556, Seq. Id. No. 558, Seq. Id. No. 561, Seq. Id. No. 566, Seq. Id. No. 600, Seq. Id. No. 602 and Seq. Id. No. 603.

A certain embodiment of present invention provides a kit according as described herein, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 556, Seq. Id. No. 557, Seq. Id. No. 558, Seq. Id. No. 559, and Seq. Id. No. 560.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 518.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 519.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 520.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 521.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 522.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 523.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 524.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 525.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 526.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 527.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 528.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 529.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 530.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 531.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 532.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 533.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 534.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 535.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 536.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 537.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 538.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 539.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 540.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 541.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 542.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 543.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 544.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 545.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 546.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 547.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 548.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 549.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 550.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 551.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 552.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 553.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 554.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 555.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 556.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 557.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 558.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 559.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 560.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 561.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 562.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 563.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 564.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 565.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 566.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 567.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 568.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 569.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 570.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 571.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 572.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 573.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 574.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 575.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 576.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 577.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 578.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 579.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 580.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 581.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 582.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 583.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 584.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 585.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 586.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 587.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 588.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 589.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 590.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 591.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 592.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 593.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 594.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 595.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 596.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 597.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 598.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 599.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 600.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 601.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 602.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 603.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 604.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 605.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 606.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 607.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 608.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 609.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 610.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 611.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 612.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 613.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 614.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 615.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 616.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 617.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 618.

A certain embodiment of present invention provides a method as described herein, wherein the autoantibody recognizes an EGFR peptide of Seq. Id. No. 619.

A certain embodiment of present invention provides a method as described herein, wherein the level of an autoantibody recognizing p53 is measured.

A certain embodiment of present invention provides a method for determining the EGFR mutation status in a tumor tissue of a human subject suffering from non-small cell lung cancer comprising:

detecting in a blood sample of a human being suffering from non-small cell lung cancer an autoantibody selected from the group of autoantibodies recognizing an human EGFR peptide as described herein, wherein the presence of said autoantibody is indicative for the presence of a mutation of exon 19 in the gene encoding EGFR in human tissue.

A certain embodiment of present invention provides a method for determining the EGFR mutation status in a tumor tissue of a human subject suffering from non-small cell lung cancer comprising:

detecting in a blood sample of a human being suffering from non-small cell lung cancer an autoantibody selected from the group of autoantibodies recognizing an human EGFR peptide as described herein, wherein the presence of said autoantibody is indicative for the presence of a deletion of exon 21 in the gene encoding EGFR in human tissue.

A certain embodiment of present invention provides a kit for detecting in a blood sample of the human subject a level of one or more autoantibodies selected from the group of autoantibodies recognizing human EGFR, wherein an increased level of said autoantibodies selected from the group of autoantibodies recognizing human EGFR in the blood sample of the human subject compared to a level of said autoantibodies representative for a human subject of a healthy population is indicative for non-small cell lung cancer.

A certain embodiment of present invention provides a kit according as described herein, wherein the autoantibody recognizes an EGFR peptide that is selected from Seq. Id. No. 1-Seq. Id. No. 15.

A certain embodiment of present invention provides a kit according as described herein, wherein the autoantibody recognizes an EGFR peptide that is selected from Seq. Id. No. 16-Seq. Id. No. 517.

A certain embodiment of present invention provides a kit according as described herein, wherein the autoantibody recognizes an EGFR peptide that is selected from Seq. Id. No. 518-Seq. Id. No. 602.

A certain embodiment of present invention provides a kit according as described herein, wherein the autoantibody recognizes an EGFR peptide that is selected from Seq. Id. No. 603-Seq. Id. No. 619.

A certain embodiment of present invention provides a kit according as described herein, wherein the autoantibody recognizes an EGFR peptide that is selected from Seq. Id. No. 519, Seq. Id. No. 520, Seq. Id. No. 521, and Seq. Id. No. 561.

FIGURES AND SEQ. ID. NUMBERS

FIG. 1: Log-transformed values of peptide binding for all peptides grouped by patient (49 samples, 4-digit numbers) and controls (1-digit numbers). Patients have on average higher signals, with a number of antibodies binding to peptides stronger than any signal in control sera.

FIG. 2: Histogram of distribution of the p-values for the significance of the antibody titers in a Cox regression model of OS or PFS˜EGFR+TRT+EGFR:TRT+SEX+Antibody titer+ Antibody titer:TRT. If antibody titers do not affect survival, a uniform distribution is expected. The deviation from the uniform distribution is highly significant, which lead to the conclusion that approximately 50% of the 245 antibody titers with p-values<0.05 will have a significant influence on progression free survival. A similar model calculation for overall survival (OS) yields 663 candidates at p-Values<0.05 with a slightly better false discovery rate of approximately 40%.

FIG. 3: Venn diagrams illustrating the refinement of peptide candidates for (A) progression free survival and (B) overall survival. Pep—initial peptide selection form Cox-regression model with all covariates; RASH: overlapping sequences from peptides predicting PFS (OS) in patients with rash in a proportional hazard model; TRT: overlapping sequences from peptides predicting PFS (OS) in the erlotinib subgroup; EC4: univariate test of response (after 4 cycles, categorical) vs. antibody titer.

FIG. 4: Presence of autoantibodies against a mutated EGFR peptide predicts (p=0.006) a better treatment outcome in the Tarceva® arm of the trial independent of the occurrence of rash.

TABLE 4

Seq. Id. No. 1-619 of human EGFR

peptides, *indicates mutated EGFR

Seq.

Id. No.
protein sequence

1*
GEKVKIPVAIKPKANK

2*
GEKVKIPVAIKSPKANK

3
KEYHAEGGKVPIKWM

4*
KIPVAIKHPTSPK

5*
KIPVAIKKPTSPK

6*
KIPVAIKPTSPK

7*
KIPVAIKRPTSPK

8
MPFGCLLDYVREH

9
NSTFDSPAHWAQKGSHQI

10
PREFVENSECIQCHPECL

11
RGPDNCIQCAHYIDGPHCVKTCP

12
RMHLPSPTDSNFYRA

13
SIDDTFLPVPEYIN

14
VRKCKKCEGPCRKV

15*
VRKSKKSEGPSRKV

16*
ADKDILDEAYVMACA

17*
ADKDILDEAYVMACG

18*
ADKDILDEAYVMACV

19*
ADKDILDEAYVMAIA

20*
ADKDILDEAYVMAIG

21*
ADKDILDEAYVMAIV

22*
ADKDILDEAYVMANA

23*
ADKDILDEAYVMANG

24*
ADKDILDEAYVMANV

25*
ADKDILDEAYVMASA

26*
ADKDILDEAYVMASG

27*
ADKDILDEAYVMASV

28*
ADKDILDEAYVMTCA

29*
ADKDILDEAYVMTCG

30*
ADKDILDEAYVMTCV

31*
ADKDILDEAYVMTIA

32*
ADKDILDEAYVMTIG

33*
ADKDILDEAYVMTIV

34*
ADKDILDEAYVMTNA

35*
ADKDILDEAYVMTNG

36*
ADKDILDEAYVMTNV

37*
ADKDILDEAYVMTSA

38*
ADKDILDEAYVMTSG

39*
ADKDILDEAYVMTSV

40*
ADKEILDEAYVMACA

41*
ADKEILDEAYVMACG

42*
ADKEILDEAYVMACV

43*
ADKEILDEAYVMAIA

44*
ADKEILDEAYVMAIG

45*
ADKEILDEAYVMAIV

46*
ADKEILDEAYVMANA

47*
ADKEILDEAYVMANG

48*
ADKEILDEAYVMANV

49*
ADKEILDEAYVMASA

50*
ADKEILDEAYVMASG

51*
ADKEILDEAYVMASV

52*
ADKEILDEAYVMTCA

53*
ADKEILDEAYVMTCG

54*
ADKEILDEAYVMTCV

55*
ADKEILDEAYVMTIA

56*
ADKEILDEAYVMTIG

57*
ADKEILDEAYVMTIV

58*
ADKEILDEAYVMTNA

59*
ADKEILDEAYVMTNG

60*
ADKEILDEAYVMTNV

61*
ADKEILDEAYVMTSA

62*
ADKEILDEAYVMTSG

63*
ADKEILDEAYVMTSV

64
AIKELREATSPKA

65*
AIKILREATSPKA

66*
AIKVLREATSPKA

67*
ANKDILDEAYVMACA

68*
ANKDILDEAYVMACG

69*
ANKDILDEAYVMACV

70*
ANKDILDEAYVMAIA

71*
ANKDILDEAYVMAIG

72*
ANKDILDEAYVMAIV

73*
ANKDILDEAYVMANA

74*
ANKDILDEAYVMANG

75*
ANKDILDEAYVMANV

76*
ANKDILDEAYVMASA

77*
ANKDILDEAYVMASG

78*
ANKDILDEAYVMASV

79*
ANKDILDEAYVMTCA

80*
ANKDILDEAYVMTCG

81*
ANKDILDEAYVMTCV

82*
ANKDILDEAYVMTIA

83*
ANKDILDEAYVMTIG

84*
ANKDILDEAYVMTIV

85*
ANKDILDEAYVMTNA

86*
ANKDILDEAYVMTNG

87*
ANKDILDEAYVMTNV

88*
ANKDILDEAYVMTSA

89*
ANKDILDEAYVMTSG

90*
ANKDILDEAYVMTSV

91*
ANKEILDEAYVMACA

92*
ANKEILDEAYVMACG

93*
ANKEILDEAYVMACV

94*
ANKEILDEAYVMAIA

95*
ANKEILDEAYVMAIG

96*
ANKEILDEAYVMAIV

97*
ANKEILDEAYVMANA

98*
ANKEILDEAYVMANG

99*
ANKEILDEAYVMANV

100*
ANKEILDEAYVMASA

101*
ANKEILDEAYVMASG

102
ANKEILDEAYVMASV

103*
ANKEILDEAYVMTCA

104*
ANKEILDEAYVMTCG

105*
ANKEILDEAYVMTCV

106*
ANKEILDEAYVMTIA

107*
ANKEILDEAYVMTIG

108*
ANKEILDEAYVMTIV

109*
ANKEILDEAYVMTNA

110*
ANKEILDEAYVMTNG

111*
ANKEILDEAYVMTNV

112*
ANKEILDEAYVMTSA

113*
ANKEILDEAYVMTSG

114*
ANKEILDEAYVMTSV

115*
ASKDILDEAYVMACA

116*
ASKDILDEAYVMACG

117*
ASKDILDEAYVMACV

118*
ASKDILDEAYVMAIA

119*
ASKDILDEAYVMAIG

120*
ASKDILDEAYVMAIV

121*
ASKDILDEAYVMANA

122*
ASKDILDEAYVMANG

123*
ASKDILDEAYVMANV

124*
ASKDILDEAYVMASA

125*
ASKDILDEAYVMASG

126*
ASKDILDEAYVMASV

127*
ASKDILDEAYVMTCA

128*
ASKDILDEAYVMTCG

129*
ASKDILDEAYVMTCV

130*
ASKDILDEAYVMTIA

131*
ASKDILDEAYVMTIG

132*
ASKDILDEAYVMTIV

133*
ASKDILDEAYVMTNA

134*
ASKDILDEAYVMTNG

135*
ASKDILDEAYVMTNV

136*
ASKDILDEAYVMTSA

137*
ASKDILDEAYVMTSG

138*
ASKDILDEAYVMTSV

139*
ASKEILDEAYVMACA

140*
ASKEILDEAYVMACG

141*
ASKEILDEAYVMACV

142*
ASKEILDEAYVMAIA

143*
ASKEILDEAYVMAIG

144*
ASKEILDEAYVMAIV

145*
ASKEILDEAYVMANA

146*
ASKEILDEAYVMANG

147*
ASKEILDEAYVMANV

148*
ASKEILDEAYVMASA

149*
ASKEILDEAYVMASG

150*
ASKEILDEAYVMASV

151*
ASKEILDEAYVMTCA

152*
ASKEILDEAYVMTCG

153*
ASKEILDEAYVMTCV

154*
ASKEILDEAYVMTIA

155*
ASKEILDEAYVMTIG

156*
ASKEILDEAYVMTIV

157*
ASKEILDEAYVMTNA

158*
ASKEILDEAYVMTNG

159*
ASKEILDEAYVMTNV

160*
ASKEILDEAYVMTSA

161*
ASKEILDEAYVMTSG

162*
ASKEILDEAYVMTSV

163*
CLLVHRDLAARNV

164*
CRLVHRDLAARNV

165*
DDKDILDEAYVMACA

166*
DDKDILDEAYVMACG

167*
DDKDILDEAYVMACV

168*
DDKDILDEAYVMAIA

169*
DDKDILDEAYVMAIG

170*
DDKDILDEAYVMAIV

171*
DDKDILDEAYVMANA

172*
DDKDILDEAYVMANG

173*
DDKDILDEAYVMANV

174*
DDKDILDEAYVMASA

175*
DDKDILDEAYVMASG

176*
DDKDILDEAYVMASV

177*
DDKDILDEAYVMTCA

178*
DDKDILDEAYVMTCG

179*
DDKDILDEAYVMTCV

180*
DDKDILDEAYVMTIA

181*
DDKDILDEAYVMTIG

182*
DDKDILDEAYVMTIV

183*
DDKDILDEAYVMTNA

184*
DDKDILDEAYVMTNG

185*
DDKDILDEAYVMTNV

186*
DDKDILDEAYVMTSA

187*
DDKDILDEAYVMTSG

188*
DDKDILDEAYVMTSV

189*
DDKEILDEAYVMACA

190*
DDKEILDEAYVMACG

191*
DDKEILDEAYVMACV

192*
DDKEILDEAYVMAIA

193*
DDKEILDEAYVMAIG

194*
DDKEILDEAYVMAIV

195*
DDKEILDEAYVMANA

196*
DDKEILDEAYVMANG

197*
DDKEILDEAYVMANV

198*
DDKEILDEAYVMASA

199*
DDKEILDEAYVMASG

200*
DDKEILDEAYVMASV

201*
DDKEILDEAYVMTCA

202*
DDKEILDEAYVMTCG

203*
DDKEILDEAYVMTCV

204*
DDKEILDEAYVMTIA

205*
DDKEILDEAYVMTIG

206*
DDKEILDEAYVMTIV

207*
DDKEILDEAYVMTNA

208*
DDKEILDEAYVMTNG

209*
DDKEILDEAYVMTNV

210*
DDKEILDEAYVMTSA

211*
DDKEILDEAYVMTSG

212*
DDKEILDEAYVMTSV

213*
DNKDILDEAYVMACA

214*
DNKDILDEAYVMACG

215*
DNKDILDEAYVMACV

216*
DNKDILDEAYVMAIA

217*
DNKDILDEAYVMAIG

218*
DNKDILDEAYVMAIV

219*
DNKDILDEAYVMANA

220*
DNKDILDEAYVMANG

221*
DNKDILDEAYVMANV

222*
DNKDILDEAYVMASA

223*
DNKDILDEAYVMASG

224*
DNKDILDEAYVMASV

225*
DNKDILDEAYVMTCA

226*
DNKDILDEAYVMTCG

227*
DNKDILDEAYVMTCV

228*
DNKDILDEAYVMTIA

229*
DNKDILDEAYVMTIG

230*
DNKDILDEAYVMTIV

231*
DNKDILDEAYVMTNA

232*
DNKDILDEAYVMTNG

233*
DNKDILDEAYVMTNV

234*
DNKDILDEAYVMTSA

235*
DNKDILDEAYVMTSG

236*
DNKDILDEAYVMTSV

237*
DNKEILDEAYVMACA

238*
DNKEILDEAYVMACG

239*
DNKEILDEAYVMACV

240*
DNKEILDEAYVMAIA

241*
DNKEILDEAYVMAIG

242*
DNKEILDEAYVMAIV

243*
DNKEILDEAYVMANA

244*
DNKEILDEAYVMANG

245*
DNKEILDEAYVMANV

246*
DNKEILDEAYVMASA

247*
DNKEILDEAYVMASG

248*
DNKEILDEAYVMASV

249*
DNKEILDEAYVMTCA

250*
DNKEILDEAYVMTCG

251*
DNKEILDEAYVMTCV

252*
DNKEILDEAYVMTIA

253*
DNKEILDEAYVMTIG

254*
DNKEILDEAYVMTIV

255*
DNKEILDEAYVMTNA

256*
DNKEILDEAYVMTNG

257*
DNKEILDEAYVMTNV

258*
DNKEILDEAYVMTSA

259*
DNKEILDEAYVMTSG

260*
DNKEILDEAYVMTSV

261*
DSKDILDEAYVMACA

262*
DSKDILDEAYVMACG

263*
DSKDILDEAYVMACV

264*
DSKDILDEAYVMAIA

265*
DSKDILDEAYVMAIG

266*
DSKDILDEAYVMAIV

267*
DSKDILDEAYVMANA

268*
DSKDILDEAYVMANG

269*
DSKDILDEAYVMANV

270*
DSKDILDEAYVMASA

271*
DSKDILDEAYVMASG

272*
DSKDILDEAYVMASV

273*
DSKDILDEAYVMTCA

274*
DSKDILDEAYVMTCG

275*
DSKDILDEAYVMTCV

276*
DSKDILDEAYVMTIA

277*
DSKDILDEAYVMTIG

278*
DSKDILDEAYVMTIV

279*
DSKDILDEAYVMTNA

280*
DSKDILDEAYVMTNG

281*
DSKDILDEAYVMTNV

282*
DSKDILDEAYVMTSA

283*
DSKDILDEAYVMTSG

284*
DSKDILDEAYVMTSV

285*
DSKEILDEAYVMACA

286*
DSKEILDEAYVMACG

287*
DSKEILDEAYVMACV

288*
DSKEILDEAYVMAIA

289*
DSKEILDEAYVMAIG

290*
DSKEILDEAYVMAIV

291*
DSKEILDEAYVMANA

292*
DSKEILDEAYVMANG

293*
DSKEILDEAYVMANV

294*
DSKEILDEAYVMASA

295*
DSKEILDEAYVMASG

296*
DSKEILDEAYVMASV

297*
DSKEILDEAYVMTCA

298*
DSKEILDEAYVMTCG

299*
DSKEILDEAYVMTCV

300*
DSKEILDEAYVMTIA

301*
DSKEILDEAYVMTIG

302*
DSKEILDEAYVMTIV

303*
DSKEILDEAYVMTNA

304*
DSKEILDEAYVMTNG

305*
DSKEILDEAYVMTNV

306*
DSKEILDEAYVMTSA

307*
DSKEILDEAYVMTSG

308*
DSKEILDEAYVMTSV

309
HYQDPHSTAVGNPEY

310*
KVKIPVAIAPSPKA

311*
KVKIPVAIATSPKA

312*
KVKIPVAIEAPSPKA

313*
KVKIPVAIEATSPKA

314*
KVKIPVAIEEAPSPKA

315*
KVKIPVAIEEATSPKA

316*
KVKIPVAIEEPSPKA

317*
KVKIPVAIEETSPKA

318*
KVKIPVAIEPSPKA

319*
KVKIPVAIERAPSPKA

320*
KVKIPVAIERATSPKA

321*
KVKIPVAIEREAPSPKA

322*
KVKIPVAIEREATSPKA

323*
KVKIPVAIEREPSPKA

324*
KVKIPVAIERETSPKA

325*
KVKIPVAIERPSPKA

326*
KVKIPVAIERTSPKA

327*
KVKIPVAIETSPKA

328*
KVKIPVAIKAPSPKA

329*
KVKIPVAIKATSPKA

330*
KVKIPVAIKEAPSPKA

331*
KVKIPVAIKEATSPKA

332*
KVKIPVAIKEEAPSPKA

333*
KVKIPVAIKEEATSPKA

334*
KVKIPVAIKEEPSPKA

335*
KVKIPVAIKEETSPKA

336*
KVKIPVAIKEPSPKA

337*
KVKIPVAIKERAPSPKA

338*
KVKIPVAIKERATSPKA

339*
KVKIPVAIKEREAPSPKA

340*
KVKIPVAIKEREATSPKA

341*
KVKIPVAIKEREPSPKA

342*
KVKIPVAIKERETSPKA

343*
KVKIPVAIKERPSPKA

344*
KVKIPVAIKERTSPKA

345*
KVKIPVAIKETSPKA

346*
KVKIPVAIKPSPKA

347*
KVKIPVAIKRAPSPKA

348*
KVKIPVAIKRATSPKA

349*
KVKIPVAIKREAPSPKA

350*
KVKIPVAIKREATSPKA

351*
KVKIPVAIKREPSPKA

352*
KVKIPVAIKRETSPKA

353*
KVKIPVAIKRPSPKA

354*
KVKIPVAIKRTSPKA

355*
KVKIPVAIKTSPKA

356*
KVKIPVAIPSPKA

357*
KVKIPVAIRAPSPKA

358*
KVKIPVAIRATSPKA

359*
KVKIPVAIREAPSPKA

360*
KVKIPVAIREATSPKA

361*
KVKIPVAIREP SPKA

362*
KVKIPVAIRETSPKA

363*
KVKIPVAIRPSPKA

364*
KVKIPVAIRTSPKA

365*
KVKIPVAITSPKA

366*
LREEILDEAYVMA

367*
LREPILDEAYVMA

368*
PEGEKAKIPVAIKELREA

369*
PEGEKAKIPVAIRELREA

370
PEGEKVKIPVAIKELREA

371*
PEGEKVKIPVAIRELREA

372*
RLLVHRDLAARNV

373
RRLVHRDLAARNV

374*
SDKDILDEAYVMACA

375*
SDKDILDEAYVMACG

376*
SDKDILDEAYVMACV

377*
SDKDILDEAYVMAIA

378*
SDKDILDEAYVMAIG

379*
SDKDILDEAYVMAIV

380*
SDKDILDEAYVMANA

381*
SDKDILDEAYVMANG

382*
SDKDILDEAYVMANV

383*
SDKDILDEAYVMASA

384*
SDKDILDEAYVMASG

385*
SDKDILDEAYVMASV

386*
SDKDILDEAYVMTCA

387*
SDKDILDEAYVMTCG

388*
SDKDILDEAYVMTCV

389*
SDKDILDEAYVMTIA

390*
SDKDILDEAYVMTIG

391*
SDKDILDEAYVMTIV

392*
SDKDILDEAYVMTNA

393*
SDKDILDEAYVMTNG

394*
SDKDILDEAYVMTNV

395*
SDKDILDEAYVMTSA

396*
SDKDILDEAYVMTSG

397*
SDKDILDEAYVMTSV

398*
SDKEILDEAYVMACA

399*
SDKEILDEAYVMACG

400*
SDKEILDEAYVMACV

401*
SDKEILDEAYVMAIA

402*
SDKEILDEAYVMAIG

403*
SDKEILDEAYVMAIV

404*
SDKEILDEAYVMANA

405*
SDKEILDEAYVMANG

406*
SDKEILDEAYVMANV

407*
SDKEILDEAYVMASA

408*
SDKEILDEAYVMASG

409*
SDKEILDEAYVMASV

410*
SDKEILDEAYVMTCA

411*
SDKEILDEAYVMTCG

412*
SDKEILDEAYVMTCV

413*
SDKEILDEAYVMTIA

414*
SDKEILDEAYVMTIG

415*
SDKEILDEAYVMTIV

416*
SDKEILDEAYVMTNA

417*
SDKEILDEAYVMTNG

418*
SDKEILDEAYVMTNV

419*
SDKEILDEAYVMTSA

420*
SDKEILDEAYVMTSG

421*
SDKEILDEAYVMTSV

422*
SNKDILDEAYVMACA

423*
SNKDILDEAYVMACG

424*
SNKDILDEAYVMACV

425*
SNKDILDEAYVMAIA

426*
SNKDILDEAYVMAIG

427*
SNKDILDEAYVMAIV

428*
SNKDILDEAYVMANA

429*
SNKDILDEAYVMANG

430*
SNKDILDEAYVMANV

431*
SNKDILDEAYVMASA

432*
SNKDILDEAYVMASG

433*
SNKDILDEAYVMASV

434*
SNKDILDEAYVMTCA

435*
SNKDILDEAYVMTCG

436*
SNKDILDEAYVMTCV

437*
SNKDILDEAYVMTIA

438*
SNKDILDEAYVMTIG

439*
SNKDILDEAYVMTIV

440*
SNKDILDEAYVMTNA

441*
SNKDILDEAYVMTNG

442*
SNKDILDEAYVMTNV

443*
SNKDILDEAYVMTSA

444*
SNKDILDEAYVMTSG

445*
SNKDILDEAYVMTSV

446*
SNKEILDEAYVMACA

447*
SNKEILDEAYVMACG

448*
SNKEILDEAYVMACV

449*
SNKEILDEAYVMAIA

450*
SNKEILDEAYVMAIG

451*
SNKEILDEAYVMAIV

452*
SNKEILDEAYVMANA

453*
SNKEILDEAYVMANG

454*
SNKEILDEAYVMANV

455*
SNKEILDEAYVMASA

456*
SNKEILDEAYVMASG

457*
SNKEILDEAYVMASV

458*
SNKEILDEAYVMTCA

459*
SNKEILDEAYVMTCG

460*
SNKEILDEAYVMTCV

461*
SNKEILDEAYVMTIA

462*
SNKEILDEAYVMTIG

463*
SNKEILDEAYVMTIV

464*
SNKEILDEAYVMTNA

465*
SNKEILDEAYVMTNG

466*
SNKEILDEAYVMTNV

467*
SNKEILDEAYVMTSA

468*
SNKEILDEAYVMTSG

469*
SNKEILDEAYVMTSV

470*
SSKDILDEAYVMACA

471*
SSKDILDEAYVMACG

472*
SSKDILDEAYVMACV

473*
SSKDILDEAYVMAIA

474*
SSKDILDEAYVMAIG

475*
SSKDILDEAYVMAIV

476*
SSKDILDEAYVMANA

477*
SSKDILDEAYVMANG

478*
SSKDILDEAYVMANV

479*
SSKDILDEAYVMASA

480*
SSKDILDEAYVMASG

481*
SSKDILDEAYVMASV

482*
SSKDILDEAYVMTCA

483*
SSKDILDEAYVMTCG

484*
SSKDILDEAYVMTCV

485*
SSKDILDEAYVMTIA

486*
SSKDILDEAYVMTIG

487*
SSKDILDEAYVMTIV

488*
SSKDILDEAYVMTNA

489*
SSKDILDEAYVMTNG

490*
SSKDILDEAYVMTNV

491*
SSKDILDEAYVMTSA

492*
SSKDILDEAYVMTSG

493*
SSKDILDEAYVMTSV

494*
SSKEILDEAYVMACA

495*
SSKEILDEAYVMACG

496*
SSKEILDEAYVMACV

497*
SSKEILDEAYVMAIA

498*
SSKEILDEAYVMAIG

499*
SSKEILDEAYVMAIV

500*
SSKEILDEAYVMANA

501*
SSKEILDEAYVMANG

502*
SSKEILDEAYVMANV

503*
SSKEILDEAYVMASA

504*
SSKEILDEAYVMASG

505*
SSKEILDEAYVMASV

506*
SKEILDEAYVMTCA

507*
SSKEILDEAYVMTCG

508*
SSKEILDEAYVMTCV

509*
SSKEILDEAYVMTIA

510*
SSKEILDEAYVMTIG

511*
SSKEILDEAYVMTIV

512*
SSKEILDEAYVMTNA

513*
SSKEILDEAYVMTNG

514*
SSKEILDEAYVMTNV

515*
SSKEILDEAYVMTSA

516*
SSKEILDEAYVMTSG

517*
SSKEILDEAYVMTSV

518*
AVVMASVDNPHVCR

519
AYVMASVDNPHVCR

520
CTGPGLEGCPTNG

521
DEAYVMASVDNPHVCRLLG

522*
ILKETEFKKIFVLGPGAFGT

523*
ILKETEFKKIFVLGSGAFGT

524*
ILKETEFKKIKVLGPGAFGT

525
ILKETEFKKIKVLGSGAFGT

526*
ILKETEFKKLFVLGPGAFGT

527*
ILKETEFKKLFVLGSGAFGT

528*
ILKETEFKKLKVLGPGAFGT

529*
ILKETEFKKLKVLGSGAFGT

530*
ILKETELKKIFVLGPGAFGT

531*
ILKETELKKIFVLGSGAFGT

532*
ILKETELKKIKVLGPGAFGT

533*
ILKETELKKIKVLGSGAFGT

534*
ILKETELKKLFVLGPGAFGT

535*
ILKETELKKLFVLGSGAFGT

536*
ILKETELKKLKVLGPGAFGT

537*
ILKETELKKLKVLGSGAFGT

538*
ILMETEFKKIFVLGPGAFGT

539*
ILMETEFKKIFVLGSGAFGT

540*
ILMETEFKKIKVLGPGAFGT

541*
ILMETEFKKIKVLGSGAFGT

542*
ILMETEFKKLFVLGPGAFGT

543*
ILMETEFKKLFVLGSGAFGT

544*
ILMETEFKKLKVLGPGAFGT

545*
ILMETEFKKLKVLGSGAFGT

546*
ILMETELKKIFVLGPGAFGT

547*
ILMETELKKIFVLGSGAFGT

548*
ILMETELKKIKVLGPGAFGT

549*
ILMETELKKIKVLGSGAFGT

550*
ILMETELKKLFVLGPGAFGT

551*
ILMETELKKLFVLGSGAFGT

552*
ILMETELKKLKVLGPGAFGT

553*
ILMETELKKLKVLGSGAFGT

554*
KGNYVVTDHGSCVRA

555*
KVKIPVAIKAPKA

556
KVKIPVAIKELREATSPKA

557*
KVKIPVAIKSPKA

558
LLRILKETEFKKI

559*
LLRILKETESKKI

560*
MNYLEDRLLVHRD

561
MNYLEDRRLVHRD

562*
RLLQERELLEPLTPSGEAPNQAFLR

563*
RLLQERELLEPLTPSGEAPNQALLR

564*
RLLQERELLEPLTPSGEAPNQAPLR

565*
RLLQERELVEPLTPSGEAPNQAFLR

566
RLLQERELVEPLTPSGEAPNQALLR

567*
RLLQERELVEPLTPSGEAPNQAPLR

568*
TLKETEFKKIFVLGPGAFGT

569*
TLKETEFKKIFVLGSGAFGT

570*
TLKETEFKKIKVLGPGAFGT

571*
TLKETEFKKIKVLGSGAFGT

572*
TLKETEFKKLFVLGPGAFGT

573*
TLKETEFKKLFVLGSGAFGT

574*
TLKETEFKKLKVLGPGAFGT

575*
TLKETEFKKLKVLGSGAFGT

576*
TLKETELKKIFVLGPGAFGT

577*
TLKETELKKIFVLGSGAFGT

578*
TLKETELKKIKVLGPGAFGT

579*
TLKETELKKIKVLGSGAFGT

580*
TLKETELKKLFVLGPGAFGT

581*
TLKETELKKLFVLGSGAFGT

582*
TLKETELKKLKVLGPGAFGT

583*
TLKETELKKLKVLGSGAFGT

584*
TLMETEFKKIFVLGPGAFGT

585*
TLMETEFKKIFVLGSGAFGT

586*
TLMETEFKKIKVLGPGAFGT

587*
TLMETEFKKIKVLGSGAFGT

588*
TLMETEFKKLFVLGPGAFGT

589*
TLMETEFKKLFVLGSGAFGT

590*
TLMETEFKKLKVLGPGAFGT

591*
TLMETEFKKLKVLGSGAFGT

592*
TLMETELKKIFVLGPGAFGT

593*
TLMETELKKIFVLGSGAFGT

594*
TLMETELKKIKVLGPGAFGT

595*
TLMETELKKIKVLGSGAFGT

596*
TLMETELKKLFVLGPGAFGT

597*
TLMETELKKLFVLGSGAFGT

598*
TLMETELKKLKVLGPGAFGT

599*
TLMETELKKLKVLGSGAFGT

600
VKITDFGLAKLLGA

601*
VKITDFGRAKLLGA

602
YLEDRRLVHRDLA

603
KVKIPVAIKELREATSPKA

604*
KVKIPVAIKAPKA

605*
KVKIPVAIKAPTS

606*
KVKIPVAIKDPKA

607*
KVKIPVAIKELKA

608*
KVKIPVAIKEPKA

609*
KVKIPVAIKEQKA

610*
KVKIPVAIKESKA

611*
KVKIPVAIKEVPK

612*
KVKIPVAIKIPKA

613*
KVKIPVAIKSPKA

614*
KVKIPVAIKTPKA

615*
KIPVAIKEASPKA

616*
KIPVAIKEFSPKA

617*
KIPVAIKENSPKA

618*
KIPVAIKVASPKA

619*
KIPVAIKVPSPKA

Experiments
Peptide Arrays

Peptide arrays were created by PepStar™ (JPT Peptide Technologies GmbH, Berlin, Germany) peptide microarray platform to generate customized peptide microarrays on glass slides for biomarker discovery, immunomonitoring and detection and validation of protein interactions. Peptides are immobilized on glass slides via a flexible linker. Chemoselective coupling generates microarrays of directed and covalently attached peptides.

3661 specified native peptides with 500 scrambled control sequences covering the sequences of EGF-receptor, Arachidonate 15-lipoxygenase B (LX15B) and p53 and variants thereof were synthesized and arrays printed. A serum dilution 1:200 was used for the detection of EGFR binding in NSCLC patient samples. Incubation of microarrays was performed in an automated Hybridization Station HS4800 (Tecan) at 30° C. After washing, bound immunoglobine G (IgG) was detected with Cy5—labeled-anti-human secondary antibody (JIR, 0.1 μg/ml end-conc. in assay). Fluorescence was read using a Microarray Scanner GenePix with Autoloader 4200AL (Molecular Devices). Signal intensity is displayed as relative fluorescence units.

The following tables detail the wash and incubation conditions:

TABLE 5

experimental conditions

Blocking Solution:
SmartBlock Blocking Buffer

Diluent for Serum and 2nd AB:
SuperBlock T20 Blocking Buffer

Wash Buffer 1:
1x TBS + 0.1% Tween 20

Wash Buffer 2:
0.1x SSC + 0.05% Tween 20

TABLE 6

experimental conditions

Step
Procedure
Parameters
Buffer

1
Wash
1x
1x TBS-0, 1% Tween20

2
Probe injection 1

Blocking Solution

3
Hybridization
1 h, 30° C.

4
Wash
2x
1x TBS-0, 1% Tween20

5
Probe injection 2
1:200
Patient Serum

6
Hybridization
2 h, 30° C.

7
Wash
3x
1x TBS-0, 1% Tween20

8
Probe injection 3

Cy5-anti-human Secondary Antibody

9
Hybridization
45 min.,

30° C.

10
Wash
2x
1x TBS-0, 1% Tween20

11
Wash
3x
0.1x SSC-0.05% Tween20

12
Slide drying
20 sec

13
Wash
3x
0.1x SSC-0.05% Tween20

14
Slide drying
5 min.

Samples

Samples were selected from patients belonging to the TASK study. TASK was a 200-patient randomized, open label, Phase II study of Tarceva® in combination with Avastin® (bevazizumab) compared to standard chemotherapy regimens (gemcitabine plus cisplatin or paclitaxel plus carboplatin) plus Avastin® in first-line NSCLC patients. Further enrollment on this study was halt after data from a pre-planned interim analysis of the first 120 patients. Occurrence of rash was recorded as adverse event. Biopsies from all patients were tested for the occurrence of EGFR mutations and the mutation status has been recorded.

For the peptide array study, a total of 49 patients from both arms (24 Avastin® and Tarceva® (A+T), 25 Avastin® and chemotherapy (A+C)) have been used. In the patients chosen for the A+T arm, rash occurred in 16 patients. In comparison, only 3 patients in the A+C arm developed rash. This corresponds to the expected frequency of rash, as rash is induced by erlotinib, but only to a very limited extend by chemotherapy.

Clinical data accessible included outcome data, e.g. response overall survival and progression free survival as well as the rash grade and the mutation status of EGFR as measured from a pre-treatment biopsy.

Statistical Analysis
Global Test

The following approach to model the data was applied:

- Descriptive statistics (using appropriate single variable) tests to identify covariates as candidates for a linear regression model describing the performance parameter (PFS or OS).
- Identification of the best model for efficacy parameters (survival analysis)
- Addition of antibody titer and its interaction with treatment to the model and comparison of the performance with the new variables
  
  With a general model selected, tests on antibody titers within groups of covariates of interest were conducted:
- Proportional hazard model by EGFR mutation (EGFRM), Thoracic Radiotherapy (TRT), rash of efficacy parameters vs. antibody abundance (two sample groups—low/high abundance—divided by median)
- U-tests within wild type (WT+) in A+T arm of antibody titer vs. responders/non-responders
- χ2 tests by EGFRM and TRT of responses (weeks 6, 12) vs. antibody abundance

Finally, various very similar peptide sequences that yield highly correlated antibody titers were used. For most of the reported peptide sequences, consensus sequence from a listing of all peptides with very high sequence similarity (Smith-Waterman alignment similarity score >50, using a PAM30 substitution matrix and a gap penalty of 1) was selected and antibody titers were correlated to the target titer (Spearman Rank correlation >0.75).

Claims

1. A method of diagnosis of non-small cell lung cancer in a human subject comprising: measuring in a blood sample of the human subject a level of an autoantibody selected from the group of autoantibodies recognizing mutated human EGFR, wherein an increased level of said autoantibody selected from the group of autoantibodies recognizing mutated human EGFR in the blood sample of the human subject compared to a level of said autoantibody representative for a human subject of a healthy population is indicative for non-small cell lung cancer.
2. The method according to claim 1, wherein the autoantibody recognizes a mutated EGFR peptide is selected from the group consisting of Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 556, Seq. Id. No. 557, Seq. Id. No. 558, Seq. Id. No. 559, and Seq. Id. No. 560.
3. The method according to any of claims 1-2, wherein the autoantibody recognizes a mutated EGFR peptide is selected from the group consisting of Seq. Id. No. 1, Seq. Id. No. 2, Seq. Id. No. 4, Seq. Id. No. 5, Seq. Id. No. 6, Seq. Id. No. 7, Seq. Id. No. 15, Seq. Id. No. 16, Seq. Id. No. 17, Seq. Id. No. 18, Seq. Id. No. 19, Seq. Id. No. 20, Seq. Id. No. 21, Seq. Id. No. 22, Seq. Id. No. 23, Seq. Id. No. 24, Seq. Id. No. 25, Seq. Id. No. 26, Seq. Id. No. 27, Seq. Id. No. 28, Seq. Id. No. 29, Seq. Id. No. 30, Seq. Id. No. 31, Seq. Id. No. 32, Seq. Id. No. 33, Seq. Id. No. 34, Seq. Id. No. 35, Seq. Id. No. 36, Seq. Id. No. 37, Seq. Id. No. 38, Seq. Id. No. 39, Seq. Id. No. 40, Seq. Id. No. 41, Seq. Id. No. 42, Seq. Id. No. 43, Seq. Id. No. 44, Seq. Id. No. 45, Seq. Id. No. 46, Seq. Id. No. 47, Seq. Id. No. 48, Seq. Id. No. 49, Seq. Id. No. 50, Seq. Id. No. 51, Seq. Id. No. 52, Seq. Id. No. 53, Seq. Id. No. 54, Seq. Id. No. 55, Seq. Id. No. 56, Seq. Id. No. 57, Seq. Id. No. 58, Seq. Id. No. 59, Seq. Id. No. 60, Seq. Id. No. 61, Seq. Id. No. 62, Seq. Id. No. 63, Seq. Id. No. 65, Seq. Id. No. 66, Seq. Id. No. 67, Seq. Id. No. 68, Seq. Id. No. 69, Seq. Id. No. 70, Seq. Id. No. 71, Seq. Id. No. 72, Seq. Id. No. 73, Seq. Id. No. 74, Seq. Id. No. 75, Seq. Id. No. 76, Seq. Id. No. 77, Seq. Id. No. 78, Seq. Id. No. 79, Seq. Id. No. 80, Seq. Id. No. 81, Seq. Id. No. 82, Seq. Id. No. 83, Seq. Id. No. 84, Seq. Id. No. 85, Seq. Id. No. 86, Seq. Id. No. 87, Seq. Id. No. 88, Seq. Id. No. 89, Seq. Id. No. 90, Seq. Id. No. 91, Seq. Id. No. 92, Seq. Id. No. 93, Seq. Id. No. 94, Seq. Id. No. 95, Seq. Id. No. 96, Seq. Id. No. 97, Seq. Id. No. 98, Seq. Id. No. 99, Seq. Id. No. 100, Seq. Id. No. 101, Seq. Id. No. 103, Seq. Id. No. 104, Seq. Id. No. 105, Seq. Id. No. 106, Seq. Id. No. 107, Seq. Id. No. 108, Seq. Id. No. 109, Seq. Id. No. 110, Seq. Id. No. 111, Seq. Id. No. 112, Seq. Id. No. 113, Seq. Id. No. 114, Seq. Id. No. 115, Seq. Id. No. 116, Seq. Id. No. 117, Seq. Id. No. 118, Seq. Id. No. 119, Seq. Id. No. 120, Seq. Id. No. 121, Seq. Id. No. 122, Seq. Id. No. 123, Seq. Id. No. 124, Seq. Id. No. 125, Seq. Id. No. 126, Seq. Id. No. 127, Seq. Id. No. 128, Seq. Id. No. 129, Seq. Id. No. 130, Seq. Id. No. 131, Seq. Id. No. 132, Seq. Id. No. 133, Seq. Id. No. 134, Seq. Id. No. 135, Seq. Id. No. 136, Seq. Id. No. 137, Seq. Id. No. 138, Seq. Id. No. 139, Seq. Id. No. 140, Seq. Id. No. 141, Seq. Id. No. 142, Seq. Id. No. 143, Seq. Id. No. 144, Seq. Id. No. 145, Seq. Id. No. 146, Seq. Id. No. 147, Seq. Id. No. 148, Seq. Id. No. 149, Seq. Id. No. 150, Seq. Id. No. 151, Seq. Id. No. 152, Seq. Id. No. 153, Seq. Id. No. 154, Seq. Id. No. 155, Seq. Id. No. 156, Seq. Id. No. 157, Seq. Id. No. 158, Seq. Id. No. 159, Seq. Id. No. 160, Seq. Id. No. 161, Seq. Id. No. 162, Seq. Id. No. 163, Seq. Id. No. 164, Seq. Id. No. 165, Seq. Id. No. 166, Seq. Id. No. 167, Seq. Id. No. 168, Seq. Id. No. 169, Seq. Id. No. 170, Seq. Id. No. 171, Seq. Id. No. 172, Seq. Id. No. 173, Seq. Id. No. 174, Seq. Id. No. 175, Seq. Id. No. 176, Seq. Id. No. 177, Seq. Id. No. 178, Seq. Id. No. 179, Seq. Id. No. 180, Seq. Id. No. 181, Seq. Id. No. 182, Seq. Id. No. 183, Seq. Id. No. 184, Seq. Id. No. 185, Seq. Id. No. 186, Seq. Id. No. 187, Seq. Id. No. 188, Seq. Id. No. 189, Seq. Id. No. 190, Seq. Id. No. 191, Seq. Id. No. 192, Seq. Id. No. 193, Seq. Id. No. 194, Seq. Id. No. 195, Seq. Id. No. 196, Seq. Id. No. 197, Seq. Id. No. 198, Seq. Id. No. 199, Seq. Id. No. 200, Seq. Id. No. 201, Seq. Id. No. 202, Seq. Id. No. 203, Seq. Id. No. 204, Seq. Id. No. 205, Seq. Id. No. 206, Seq. Id. No. 207, Seq. Id. No. 208, Seq. Id. No. 209, Seq. Id. No. 210, Seq. Id. No. 211, Seq. Id. No. 212, Seq. Id. No. 213, Seq. Id. No. 214, Seq. Id. No. 215, Seq. Id. No. 216, Seq. Id. No. 217, Seq. Id. No. 218, Seq. Id. No. 219, Seq. Id. No. 220, Seq. Id. No. 221, Seq. Id. No. 222, Seq. Id. No. 223, Seq. Id. No. 224, Seq. Id. No. 225, Seq. Id. No. 226, Seq. Id. No. 227, Seq. Id. No. 228, Seq. Id. No. 229, Seq. Id. No. 230, Seq. Id. No. 231, Seq. Id. No. 232, Seq. Id. No. 233, Seq. Id. No. 234, Seq. Id. No. 235, Seq. Id. No. 236, Seq. Id. No. 237, Seq. Id. No. 238, Seq. Id. No. 239, Seq. Id. No. 240, Seq. Id. No. 241, Seq. Id. No. 242, Seq. Id. No. 243, Seq. Id. No. 244, Seq. Id. No. 245, Seq. Id. No. 246, Seq. Id. No. 247, Seq. Id. No. 248, Seq. Id. No. 249, Seq. Id. No. 250, Seq. Id. No. 251, Seq. Id. No. 252, Seq. Id. No. 253, Seq. Id. No. 254, Seq. Id. No. 255, Seq. Id. No. 256, Seq. Id. No. 257, Seq. Id. No. 258, Seq. Id. No. 259, Seq. Id. No. 260, Seq. Id. No. 261, Seq. Id. No. 262, Seq. Id. No. 263, Seq. Id. No. 264, Seq. Id. No. 265, Seq. Id. No. 266, Seq. Id. No. 267, Seq. Id. No. 268, Seq. Id. No. 269, Seq. Id. No. 270, Seq. Id. No. 271, Seq. Id. No. 272, Seq. Id. No. 273, Seq. Id. No. 274, Seq. Id. No. 275, Seq. Id. No. 276, Seq. Id. No. 277, Seq. Id. No. 278, Seq. Id. No. 279, Seq. Id. No. 280, Seq. Id. No. 281, Seq. Id. No. 282, Seq. Id. No. 283, Seq. Id. No. 284, Seq. Id. No. 285, Seq. Id. No. 286, Seq. Id. No. 287, Seq. Id. No. 288, Seq. Id. No. 289, Seq. Id. No. 290, Seq. Id. No. 291, Seq. Id. No. 292, Seq. Id. No. 293, Seq. Id. No. 294, Seq. Id. No. 295, Seq. Id. No. 296, Seq. Id. No. 297, Seq. Id. No. 298, Seq. Id. No. 299, Seq. Id. No. 300, Seq. Id. No. 301, Seq. Id. No. 302, Seq. Id. No. 303, Seq. Id. No. 304, Seq. Id. No. 305, Seq. Id. No. 306, Seq. Id. No. 307, Seq. Id. No. 308, Seq. Id. No. 310, Seq. Id. No. 311, Seq. Id. No. 312, Seq. Id. No. 313, Seq. Id. No. 314, Seq. Id. No. 315, Seq. Id. No. 316, Seq. Id. No. 317, Seq. Id. No. 318, Seq. Id. No. 319, Seq. Id. No. 320, Seq. Id. No. 321, Seq. Id. No. 322, Seq. Id. No. 323, Seq. Id. No. 324, Seq. Id. No. 325, Seq. Id. No. 326, Seq. Id. No. 327, Seq. Id. No. 328, Seq. Id. No. 329, Seq. Id. No. 330, Seq. Id. No. 331, Seq. Id. No. 332, Seq. Id. No. 333, Seq. Id. No. 334, Seq. Id. No. 335, Seq. Id. No. 336, Seq. Id. No. 337, Seq. Id. No. 338, Seq. Id. No. 339, Seq. Id. 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4. The method according to any of claims 1-3, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the groups consisting of Seq. Id. No. 1, Seq. Id. No. 2, Seq. Id. No. 4, Seq. Id. No. 5, Seq. Id. No. 6, Seq. Id. No. 7 and Seq. Id. No. 15.
5. The method according to any of claims 1-3, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 16, Seq. Id. No. 17, Seq. Id. No. 18, Seq. Id. No. 19, Seq. Id. No. 20, Seq. Id. No. 21, Seq. Id. No. 22, Seq. Id. No. 23, Seq. Id. No. 24, Seq. Id. No. 25, Seq. Id. No. 26, Seq. Id. No. 27, Seq. Id. No. 28, Seq. Id. No. 29, Seq. Id. No. 30, Seq. Id. No. 31, Seq. Id. No. 32, Seq. Id. No. 33, Seq. Id. No. 34, Seq. Id. No. 35, Seq. Id. No. 36, Seq. Id. No. 37, Seq. Id. No. 38, Seq. Id. No. 39, Seq. Id. No. 40, Seq. Id. No. 41, Seq. Id. No. 42, Seq. Id. No. 43, Seq. Id. No. 44, Seq. Id. No. 45, Seq. Id. No. 46, Seq. Id. No. 47, Seq. Id. No. 48, Seq. Id. No. 49, Seq. Id. No. 50, Seq. Id. No. 51, Seq. Id. No. 52, Seq. Id. No. 53, Seq. Id. No. 54, Seq. Id. No. 55, Seq. Id. No. 56, Seq. Id. No. 57, Seq. Id. No. 58, Seq. Id. No. 59, Seq. Id. No. 60, Seq. Id. No. 61, Seq. Id. No. 62, Seq. Id. No. 63, Seq. Id. No. 65, Seq. Id. 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No. 457, Seq. Id. No. 458, Seq. Id. No. 459, Seq. Id. No. 460, Seq. Id. No. 461, Seq. Id. No. 462, Seq. Id. No. 463, Seq. Id. No. 464, Seq. Id. No. 465, Seq. Id. No. 466, Seq. Id. No. 467, Seq. Id. No. 468, Seq. Id. No. 469, Seq. Id. No. 470, Seq. Id. No. 471, Seq. Id. No. 472, Seq. Id. No. 473, Seq. Id. No. 474, Seq. Id. No. 475, Seq. Id. No. 476, Seq. Id. No. 477, Seq. Id. No. 478, Seq. Id. No. 479, Seq. Id. No. 480, Seq. Id. No. 481, Seq. Id. No. 482, Seq. Id. No. 483, Seq. Id. No. 484, Seq. Id. No. 485, Seq. Id. No. 486, Seq. Id. No. 487, Seq. Id. No. 488, Seq. Id. No. 489, Seq. Id. No. 490, Seq. Id. No. 491, Seq. Id. No. 492, Seq. Id. No. 493, Seq. Id. No. 494, Seq. Id. No. 495, Seq. Id. No. 496, Seq. Id. No. 497, Seq. Id. No. 498, Seq. Id. No. 499, Seq. Id. No. 500, Seq. Id. No. 501, Seq. Id. No. 502, Seq. Id. No. 503, Seq. Id. No. 504, Seq. Id. No. 505, Seq. Id. No. 506, Seq. Id. No. 507, Seq. Id. No. 508, Seq. Id. No. 509, Seq. Id. No. 510, Seq. Id. No. 511, Seq. Id. No. 512, Seq. Id. No. 513, Seq. Id. No. 514, Seq. Id. No. 515, Seq. Id. No. 516 and Seq. Id. No. 517.
6. The method according to any of claims 1-3, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 518, Seq. Id. No. 522, Seq. Id. No. 523, Seq. Id. No. 524, Seq. Id. No. 526, Seq. Id. No. 527, Seq. Id. No. 528, Seq. Id. No. 529, Seq. Id. No. 530, Seq. Id. No. 531, Seq. Id. No. 532, Seq. Id. No. 533, Seq. Id. No. 534, Seq. Id. No. 535, Seq. Id. No. 536, Seq. Id. No. 537, Seq. Id. No. 538, Seq. Id. No. 539, Seq. Id. No. 540, Seq. Id. No. 541, Seq. Id. No. 542, Seq. Id. No. 543, Seq. Id. No. 544, Seq. Id. No. 545, Seq. Id. No. 546, Seq. Id. No. 547, Seq. Id. No. 548, Seq. Id. No. 549, Seq. Id. No. 550, Seq. Id. No. 551, Seq. Id. No. 552, Seq. Id. No. 553, Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 557, Seq. Id. No. 559, Seq. Id. No. 560, Seq. Id. No. 562, Seq. Id. No. 563, Seq. Id. No. 564, Seq. Id. No. 565, Seq. Id. No. 567, Seq. Id. No. 568, Seq. Id. No. 569, Seq. Id. No. 570, Seq. Id. No. 571, Seq. Id. No. 572, Seq. Id. No. 573, Seq. Id. No. 574, Seq. Id. No. 575, Seq. Id. No. 576, Seq. Id. No. 577, Seq. Id. No. 578, Seq. Id. No. 579, Seq. Id. No. 580, Seq. Id. No. 581, Seq. Id. No. 582, Seq. Id. No. 583, Seq. Id. No. 584, Seq. Id. No. 585, Seq. Id. No. 586, Seq. Id. No. 587, Seq. Id. No. 588, Seq. Id. No. 589, Seq. Id. No. 590, Seq. Id. No. 591, Seq. Id. No. 592, Seq. Id. No. 593, Seq. Id. No. 594, Seq. Id. No. 595, Seq. Id. No. 596, Seq. Id. No. 597, Seq. Id. No. 598, Seq. Id. No. 599 and Seq. Id. No. 601.
7. The method according to any of claims 1-3, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 604, Seq. Id. No. 605, Seq. Id. No. 606, Seq. Id. No. 607, Seq. Id. No. 608, Seq. Id. No. 609, Seq. Id. No. 610, Seq. Id. No. 611, Seq. Id. No. 612, Seq. Id. No. 613, Seq. Id. No. 614, Seq. Id. No. 615, Seq. Id. No. 616, Seq. Id. No. 617, Seq. Id. No. 618 and Seq. Id. No. 619.
8. The method according to any of claims 1-7, wherein the level of an autoantibody in the blood sample of the human subject is 5 times higher than the level of said autoantibody representative for a human subject of a healthy population.
9. Erlotinib or a pharmaceutically acceptable salt thereof, in particular erlotinib hydrochloride, for use in treating a NSCLC patient identified by a method of any of claims 1 to 8 comprising administering erlotinib or a pharmaceutically acceptable salt thereof, in particular erlotinib hydrochloride to the patient.
10. Use of an autoantibody for predicting the response of a NSCLC patient to erlotinib or a pharmaceutically acceptable salt thereof, in particular erlotinib hydrochloride, treatment, which antibody was identified by a method of any of claims 1 to 8.
11. A kit for detecting in a blood sample of the human subject a level of one or more autoantibodies selected from the group of autoantibodies recognizing mutated human EGFR, wherein an increased level of said autoantibodies selected from the group of autoantibodies recognizing mutated human EGFR in the blood sample of the human subject compared to a level of said autoantibodies representative for a human subject of a healthy population is indicative for non-small cell lung cancer.
12. A kit according to claim 11, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 556, Seq. Id. No. 557, Seq. Id. No. 558, Seq. Id. No. 559, and Seq. Id. No. 560.
13. A kit according to claim 11, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 1, Seq. Id. No. 2, Seq. Id. No. 4, Seq. Id. No. 5, Seq. Id. No. 6, Seq. Id. No. 7 and Seq. Id. No. 15.
14. A kit according to claim 11, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 16, Seq. Id. No. 17, Seq. Id. No. 18, Seq. Id. No. 19, Seq. Id. No. 20, Seq. Id. No. 21, Seq. Id. No. 22, Seq. Id. No. 23, Seq. Id. No. 24, Seq. Id. No. 25, Seq. Id. No. 26, Seq. Id. No. 27, Seq. Id. No. 28, Seq. Id. No. 29, Seq. Id. No. 30, Seq. Id. No. 31, Seq. Id. No. 32, Seq. Id. No. 33, Seq. Id. No. 34, Seq. Id. No. 35, Seq. Id. No. 36, Seq. Id. No. 37, Seq. Id. No. 38, Seq. Id. No. 39, Seq. Id. No. 40, Seq. Id. No. 41, Seq. Id. No. 42, Seq. Id. No. 43, Seq. Id. No. 44, Seq. Id. No. 45, Seq. Id. No. 46, Seq. Id. No. 47, Seq. Id. No. 48, Seq. Id. No. 49, Seq. Id. No. 50, Seq. Id. No. 51, Seq. Id. No. 52, Seq. Id. No. 53, Seq. Id. No. 54, Seq. Id. No. 55, Seq. Id. No. 56, Seq. Id. No. 57, Seq. Id. No. 58, Seq. Id. No. 59, Seq. Id. No. 60, Seq. Id. No. 61, Seq. Id. No. 62, Seq. Id. No. 63, Seq. Id. No. 65, Seq. Id. No. 66, Seq. Id. No. 67, Seq. Id. No. 68, Seq. Id. No. 69, Seq. Id. No. 70, Seq. Id. No. 71, Seq. Id. No. 72, Seq. Id. No. 73, Seq. Id. No. 74, Seq. Id. No. 75, Seq. Id. No. 76, Seq. Id. No. 77, Seq. Id. No. 78, Seq. Id. No. 79, Seq. Id. No. 80, Seq. Id. No. 81, Seq. Id. No. 82, Seq. Id. No. 83, Seq. Id. No. 84, Seq. Id. No. 85, Seq. Id. No. 86, Seq. Id. No. 87, Seq. Id. No. 88, Seq. Id. No. 89, Seq. Id. No. 90, Seq. Id. No. 91, Seq. Id. No. 92, Seq. Id. No. 93, Seq. Id. No. 94, Seq. Id. No. 95, Seq. Id. No. 96, Seq. Id. No. 97, Seq. Id. No. 98, Seq. Id. No. 99, Seq. Id. No. 100, Seq. Id. No. 101, Seq. Id. No. 103, Seq. Id. No. 104, Seq. Id. No. 105, Seq. Id. No. 106, Seq. Id. No. 107, Seq. Id. No. 108, Seq. Id. No. 109, Seq. Id. No. 110, Seq. Id. No. 111, Seq. Id. No. 112, Seq. Id. No. 113, Seq. Id. No. 114, Seq. Id. No. 115, Seq. Id. No. 116, Seq. Id. No. 117, Seq. Id. No. 118, Seq. Id. No. 119, Seq. Id. No. 120, Seq. Id. No. 121, Seq. Id. No. 122, Seq. Id. No. 123, Seq. Id. No. 124, Seq. Id. No. 125, Seq. Id. No. 126, Seq. Id. No. 127, Seq. Id. No. 128, Seq. Id. No. 129, Seq. Id. No. 130, Seq. Id. No. 131, Seq. Id. No. 132, Seq. Id. No. 133, Seq. Id. No. 134, Seq. Id. No. 135, Seq. Id. No. 136, Seq. Id. No. 137, Seq. Id. No. 138, Seq. Id. No. 139, Seq. Id. No. 140, Seq. Id. No. 141, Seq. Id. No. 142, Seq. Id. No. 143, Seq. Id. No. 144, Seq. Id. No. 145, Seq. Id. No. 146, Seq. Id. No. 147, Seq. Id. No. 148, Seq. Id. No. 149, Seq. Id. No. 150, Seq. Id. No. 151, Seq. Id. No. 152, Seq. Id. No. 153, Seq. Id. No. 154, Seq. Id. No. 155, Seq. Id. No. 156, Seq. Id. No. 157, Seq. Id. No. 158, Seq. Id. No. 159, Seq. Id. No. 160, Seq. Id. No. 161, Seq. Id. No. 162, Seq. Id. No. 163, Seq. Id. No. 164, Seq. Id. No. 165, Seq. Id. No. 166, Seq. Id. No. 167, Seq. Id. No. 168, Seq. Id. No. 169, Seq. Id. No. 170, Seq. Id. No. 171, Seq. Id. No. 172, Seq. Id. No. 173, Seq. Id. No. 174, Seq. Id. No. 175, Seq. Id. No. 176, Seq. Id. No. 177, Seq. Id. No. 178, Seq. Id. No. 179, Seq. Id. No. 180, Seq. Id. No. 181, Seq. Id. No. 182, Seq. Id. No. 183, Seq. Id. No. 184, Seq. Id. No. 185, Seq. Id. No. 186, Seq. Id. No. 187, Seq. Id. No. 188, Seq. Id. No. 189, Seq. Id. No. 190, Seq. Id. No. 191, Seq. Id. No. 192, Seq. Id. No. 193, Seq. Id. No. 194, Seq. Id. No. 195, Seq. Id. No. 196, Seq. Id. No. 197, Seq. Id. No. 198, Seq. Id. No. 199, Seq. Id. No. 200, Seq. Id. No. 201, Seq. Id. No. 202, Seq. Id. No. 203, Seq. Id. No. 204, Seq. Id. No. 205, Seq. Id. No. 206, Seq. Id. No. 207, Seq. Id. No. 208, Seq. Id. No. 209, Seq. Id. No. 210, Seq. Id. No. 211, Seq. Id. No. 212, Seq. Id. No. 213, Seq. Id. No. 214, Seq. Id. No. 215, Seq. Id. No. 216, Seq. Id. No. 217, Seq. Id. No. 218, Seq. Id. No. 219, Seq. Id. No. 220, Seq. Id. No. 221, Seq. Id. No. 222, Seq. Id. No. 223, Seq. Id. No. 224, Seq. Id. No. 225, Seq. Id. No. 226, Seq. Id. No. 227, Seq. Id. No. 228, Seq. Id. No. 229, Seq. Id. No. 230, Seq. Id. No. 231, Seq. Id. No. 232, Seq. Id. No. 233, Seq. Id. No. 234, Seq. Id. No. 235, Seq. Id. No. 236, Seq. Id. No. 237, Seq. Id. No. 238, Seq. Id. No. 239, Seq. Id. No. 240, Seq. Id. No. 241, Seq. Id. No. 242, Seq. Id. No. 243, Seq. Id. No. 244, Seq. Id. No. 245, Seq. Id. No. 246, Seq. Id. No. 247, Seq. Id. No. 248, Seq. Id. No. 249, Seq. Id. No. 250, Seq. Id. No. 251, Seq. Id. No. 252, Seq. Id. No. 253, Seq. Id. No. 254, Seq. Id. No. 255, Seq. Id. No. 256, Seq. Id. No. 257, Seq. Id. No. 258, Seq. Id. No. 259, Seq. Id. No. 260, Seq. Id. No. 261, Seq. Id. No. 262, Seq. Id. No. 263, Seq. Id. No. 264, Seq. Id. No. 265, Seq. Id. No. 266, Seq. Id. No. 267, Seq. Id. No. 268, Seq. Id. No. 269, Seq. Id. No. 270, Seq. Id. No. 271, Seq. Id. No. 272, Seq. Id. No. 273, Seq. Id. No. 274, Seq. Id. No. 275, Seq. Id. No. 276, Seq. Id. No. 277, Seq. Id. No. 278, Seq. Id. No. 279, Seq. Id. No. 280, Seq. Id. No. 281, Seq. Id. No. 282, Seq. Id. No. 283, Seq. Id. No. 284, Seq. Id. No. 285, Seq. Id. No. 286, Seq. Id. No. 287, Seq. Id. No. 288, Seq. Id. No. 289, Seq. Id. No. 290, Seq. Id. No. 291, Seq. Id. No. 292, Seq. Id. No. 293, Seq. Id. No. 294, Seq. Id. No. 295, Seq. Id. No. 296, Seq. Id. No. 297, Seq. Id. No. 298, Seq. Id. No. 299, Seq. Id. No. 300, Seq. Id. No. 301, Seq. Id. No. 302, Seq. Id. No. 303, Seq. Id. No. 304, Seq. Id. No. 305, Seq. Id. No. 306, Seq. Id. No. 307, Seq. Id. No. 308, Seq. Id. No. 310, Seq. Id. No. 311, Seq. Id. No. 312, Seq. Id. No. 313, Seq. Id. No. 314, Seq. Id. No. 315, Seq. Id. No. 316, Seq. Id. No. 317, Seq. Id. No. 318, Seq. Id. No. 319, Seq. Id. No. 320, Seq. Id. No. 321, Seq. Id. No. 322, Seq. Id. No. 323, Seq. Id. No. 324, Seq. Id. No. 325, Seq. Id. No. 326, Seq. Id. No. 327, Seq. Id. No. 328, Seq. Id. No. 329, Seq. Id. No. 330, Seq. Id. No. 331, Seq. Id. No. 332, Seq. Id. No. 333, Seq. Id. No. 334, Seq. Id. No. 335, Seq. Id. No. 336, Seq. Id. No. 337, Seq. Id. No. 338, Seq. Id. No. 339, Seq. Id. No. 340, Seq. Id. No. 341, Seq. Id. No. 342, Seq. Id. No. 343, Seq. Id. No. 344, Seq. Id. No. 345, Seq. Id. No. 346, Seq. Id. No. 347, Seq. Id. No. 348, Seq. Id. No. 349, Seq. Id. No. 350, Seq. Id. No. 351, Seq. Id. No. 352, Seq. Id. No. 353, Seq. Id. No. 354, Seq. Id. No. 355, Seq. Id. No. 356, Seq. Id. No. 357, Seq. Id. No. 358, Seq. Id. No. 359, Seq. Id. No. 360, Seq. Id. No. 361, Seq. Id. No. 362, Seq. Id. No. 363, Seq. Id. No. 364, Seq. Id. No. 365, Seq. Id. No. 366, Seq. Id. No. 367, Seq. Id. No. 368, Seq. Id. No. 369, Seq. Id. No. 371, Seq. Id. No. 372, Seq. Id. No. 374, Seq. Id. No. 375, Seq. Id. No. 376, Seq. Id. No. 377, Seq. Id. No. 378, Seq. Id. No. 379, Seq. Id. No. 380, Seq. Id. No. 381, Seq. Id. No. 382, Seq. Id. No. 383, Seq. Id. No. 384, Seq. Id. No. 385, Seq. Id. No. 386, Seq. Id. No. 387, Seq. Id. No. 388, Seq. Id. No. 389, Seq. Id. No. 390, Seq. Id. No. 391, Seq. Id. No. 392, Seq. Id. No. 393, Seq. Id. No. 394, Seq. Id. No. 395, Seq. Id. No. 396, Seq. Id. No. 397, Seq. Id. No. 398, Seq. Id. No. 399, Seq. Id. No. 400, Seq. Id. No. 401, Seq. Id. No. 402, Seq. Id. No. 403, Seq. Id. No. 404, Seq. Id. No. 405, Seq. Id. No. 406, Seq. Id. No. 407, Seq. Id. No. 408, Seq. Id. No. 409, Seq. Id. No. 410, Seq. Id. No. 411, Seq. Id. No. 412, Seq. Id. No. 413, Seq. Id. No. 414, Seq. Id. No. 415, Seq. Id. No. 416, Seq. Id. No. 417, Seq. Id. No. 418, Seq. Id. No. 419, Seq. Id. No. 420, Seq. Id. No. 421, Seq. Id. No. 422, Seq. Id. No. 423, Seq. Id. No. 424, Seq. Id. No. 425, Seq. Id. No. 426, Seq. Id. No. 427, Seq. Id. No. 428, Seq. Id. No. 429, Seq. Id. No. 430, Seq. Id. No. 431, Seq. Id. No. 432, Seq. Id. No. 433, Seq. Id. No. 434, Seq. Id. No. 435, Seq. Id. No. 436, Seq. Id. No. 437, Seq. Id. No. 438, Seq. Id. No. 439, Seq. Id. No. 440, Seq. Id. No. 441, Seq. Id. No. 442, Seq. Id. No. 443, Seq. Id. No. 444, Seq. Id. No. 445, Seq. Id. No. 446, Seq. Id. No. 447, Seq. Id. No. 448, Seq. Id. No. 449, Seq. Id. No. 450, Seq. Id. No. 451, Seq. Id. No. 452, Seq. Id. No. 453, Seq. Id. No. 454, Seq. Id. No. 455, Seq. Id. No. 456, Seq. Id. No. 457, Seq. Id. No. 458, Seq. Id. No. 459, Seq. Id. No. 460, Seq. Id. No. 461, Seq. Id. No. 462, Seq. Id. No. 463, Seq. Id. No. 464, Seq. Id. No. 465, Seq. Id. No. 466, Seq. Id. No. 467, Seq. Id. No. 468, Seq. Id. No. 469, Seq. Id. No. 470, Seq. Id. No. 471, Seq. Id. No. 472, Seq. Id. No. 473, Seq. Id. No. 474, Seq. Id. No. 475, Seq. Id. No. 476, Seq. Id. No. 477, Seq. Id. No. 478, Seq. Id. No. 479, Seq. Id. No. 480, Seq. Id. No. 481, Seq. Id. No. 482, Seq. Id. No. 483, Seq. Id. No. 484, Seq. Id. No. 485, Seq. Id. No. 486, Seq. Id. No. 487, Seq. Id. No. 488, Seq. Id. No. 489, Seq. Id. No. 490, Seq. Id. No. 491, Seq. Id. No. 492, Seq. Id. No. 493, Seq. Id. No. 494, Seq. Id. No. 495, Seq. Id. No. 496, Seq. Id. No. 497, Seq. Id. No. 498, Seq. Id. No. 499, Seq. Id. No. 500, Seq. Id. No. 501, Seq. Id. No. 502, Seq. Id. No. 503, Seq. Id. No. 504, Seq. Id. No. 505, Seq. Id. No. 506, Seq. Id. No. 507, Seq. Id. No. 508, Seq. Id. No. 509, Seq. Id. No. 510, Seq. Id. No. 511, Seq. Id. No. 512, Seq. Id. No. 513, Seq. Id. No. 514, Seq. Id. No. 515, Seq. Id. No. 516 and Seq. Id. No. 517.
15. A kit according to claim 11, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 518, Seq. Id. No. 522, Seq. Id. No. 523, Seq. Id. No. 524, Seq. Id. No. 526, Seq. Id. No. 527, Seq. Id. No. 528, Seq. Id. No. 529, Seq. Id. No. 530, Seq. Id. No. 531, Seq. Id. No. 532, Seq. Id. No. 533, Seq. Id. No. 534, Seq. Id. No. 535, Seq. Id. No. 536, Seq. Id. No. 537, Seq. Id. No. 538, Seq. Id. No. 539, Seq. Id. No. 540, Seq. Id. No. 541, Seq. Id. No. 542, Seq. Id. No. 543, Seq. Id. No. 544, Seq. Id. No. 545, Seq. Id. No. 546, Seq. Id. No. 547, Seq. Id. No. 548, Seq. Id. No. 549, Seq. Id. No. 550, Seq. Id. No. 551, Seq. Id. No. 552, Seq. Id. No. 553, Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 557, Seq. Id. No. 559, Seq. Id. No. 560, Seq. Id. No. 562, Seq. Id. No. 563, Seq. Id. No. 564, Seq. Id. No. 565, Seq. Id. No. 567, Seq. Id. No. 568, Seq. Id. No. 569, Seq. Id. No. 570, Seq. Id. No. 571, Seq. Id. No. 572, Seq. Id. No. 573, Seq. Id. No. 574, Seq. Id. No. 575, Seq. Id. No. 576, Seq. Id. No. 577, Seq. Id. No. 578, Seq. Id. No. 579, Seq. Id. No. 580, Seq. Id. No. 581, Seq. Id. No. 582, Seq. Id. No. 583, Seq. Id. No. 584, Seq. Id. No. 585, Seq. Id. No. 586, Seq. Id. No. 587, Seq. Id. No. 588, Seq. Id. No. 589, Seq. Id. No. 590, Seq. Id. No. 591, Seq. Id. No. 592, Seq. Id. No. 593, Seq. Id. No. 594, Seq. Id. No. 595, Seq. Id. No. 596, Seq. Id. No. 597, Seq. Id. No. 598, Seq. Id. No. 599 and Seq. Id. No. 601.
16. A kit according to claim 11, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 604, Seq. Id. No. 605, Seq. Id. No. 606, Seq. Id. No. 607, Seq. Id. No. 608, Seq. Id. No. 609, Seq. Id. No. 610, Seq. Id. No. 611, Seq. Id. No. 612, Seq. Id. No. 613, Seq. Id. No. 614, Seq. Id. No. 615, Seq. Id. No. 616, Seq. Id. No. 617, Seq. Id. No. 618 and Seq. Id. No. 619.
17. A method of diagnosis of non-small cell lung cancer in a human subject comprising: measuring in a blood sample of the human subject a level of an autoantibody selected from the group of autoantibodies recognizing human EGFR, wherein an increased level of said autoantibody selected from the group of autoantibodies recognizing human EGFR in the blood sample of the human subject compared to a level of said autoantibody representative for a human subject of a healthy population is indicative for non-small cell lung cancer.
18. The method according to claim 16, wherein the autoantibody recognizes a mutated EGFR peptide is selected from the group consisting of Seq. Id. No. 519, Seq. Id. No. 520, Seq. Id. No. 521 and Seq. Id. No. 561.
19. The method according to any of claims 17-18, wherein the autoantibody recognizes an EGFR peptide is selected from the group consisting of Seq. Id. No. 1, Seq. Id. No. 2, Seq. Id. No. 3, Seq. Id. No. 4, Seq. Id. No. 5, Seq. Id. No. 6, Seq. Id. No. 7, Seq. Id. No. 8, Seq. Id. No. 9, Seq. Id. No. 10, Seq. Id. No. 11, Seq. Id. No. 12, Seq. Id. No. 13, Seq. Id. No. 14, Seq. Id. No. 15, Seq. Id. No. 16, Seq. Id. No. 17, Seq. Id. No. 18, Seq. Id. No. 19, Seq. Id. No. 20, Seq. Id. No. 21, Seq. Id. No. 22, Seq. Id. No. 23, Seq. Id. No. 24, Seq. Id. No. 25, Seq. Id. No. 26, Seq. Id. No. 27, Seq. Id. No. 28, Seq. Id. No. 29, Seq. Id. No. 30, Seq. Id. No. 31, Seq. Id. No. 32, Seq. Id. No. 33, Seq. Id. No. 34, Seq. Id. No. 35, Seq. Id. No. 36, Seq. Id. No. 37, Seq. Id. No. 38, Seq. Id. No. 39, Seq. Id. No. 40, Seq. Id. No. 41, Seq. Id. No. 42, Seq. Id. No. 43, Seq. Id. No. 44, Seq. Id. No. 45, Seq. Id. No. 46, Seq. Id. No. 47, Seq. Id. No. 48, Seq. Id. No. 49, Seq. Id. No. 50, Seq. Id. No. 51, Seq. Id. No. 52, Seq. Id. No. 53, Seq. Id. No. 54, Seq. Id. No. 55, Seq. Id. No. 56, Seq. Id. No. 57, Seq. Id. No. 58, Seq. Id. No. 59, Seq. Id. No. 60, Seq. Id. No. 61, Seq. Id. No. 62, Seq. Id. No. 63, Seq. Id. No. 64, Seq. Id. No. 65, Seq. Id. No. 66, Seq. Id. No. 67, Seq. Id. No. 68, Seq. Id. No. 69, Seq. Id. No. 70, Seq. Id. No. 71, Seq. Id. No. 72, Seq. Id. No. 73, Seq. Id. No. 74, Seq. Id. No. 75, Seq. Id. No. 76, Seq. Id. No. 77, Seq. Id. No. 78, Seq. Id. No. 79, Seq. Id. No. 80, Seq. Id. No. 81, Seq. Id. No. 82, Seq. Id. No. 83, Seq. Id. No. 84, Seq. Id. No. 85, Seq. Id. No. 86, Seq. Id. No. 87, Seq. Id. No. 88, Seq. Id. No. 89, Seq. Id. No. 90, Seq. Id. No. 91, Seq. Id. No. 92, Seq. Id. No. 93, Seq. Id. No. 94, Seq. Id. No. 95, Seq. Id. No. 96, Seq. Id. No. 97, Seq. Id. No. 98, Seq. Id. No. 99, Seq. Id. No. 100, Seq. Id. No. 101, Seq. Id. No. 102, Seq. Id. No. 103, Seq. Id. No. 104, Seq. Id. No. 105, Seq. Id. No. 106, Seq. Id. No. 107, Seq. Id. No. 108, Seq. Id. No. 109, Seq. Id. No. 110, Seq. Id. No. 111, Seq. Id. No. 112, Seq. Id. No. 113, Seq. Id. No. 114, Seq. Id. No. 115, Seq. Id. No. 116, Seq. Id. No. 117, Seq. Id. No. 118, Seq. Id. No. 119, Seq. Id. No. 120, Seq. Id. No. 121, Seq. Id. No. 122, Seq. Id. No. 123, Seq. Id. No. 124, Seq. Id. No. 125, Seq. Id. No. 126, Seq. Id. No. 127, Seq. Id. No. 128, Seq. Id. No. 129, Seq. Id. No. 130, Seq. Id. No. 131, Seq. Id. No. 132, Seq. Id. No. 133, Seq. Id. No. 134, Seq. Id. No. 135, Seq. Id. No. 136, Seq. Id. No. 137, Seq. Id. No. 138, Seq. Id. No. 139, Seq. Id. No. 140, Seq. Id. No. 141, Seq. Id. No. 142, Seq. Id. No. 143, Seq. Id. No. 144, Seq. Id. No. 145, Seq. Id. No. 146, Seq. Id. No. 147, Seq. Id. No. 148, Seq. Id. No. 149, Seq. Id. No. 150, Seq. Id. No. 151, Seq. Id. No. 152, Seq. Id. No. 153, Seq. Id. No. 154, Seq. Id. No. 155, Seq. Id. No. 156, Seq. Id. No. 157, Seq. Id. No. 158, Seq. Id. No. 159, Seq. Id. No. 160, Seq. Id. No. 161, Seq. Id. No. 162, Seq. Id. No. 163, Seq. Id. No. 164, Seq. Id. No. 165, Seq. Id. No. 166, Seq. Id. No. 167, Seq. Id. No. 168, Seq. Id. No. 169, Seq. Id. No. 170, Seq. Id. No. 171, Seq. Id. No. 172, Seq. Id. No. 173, Seq. Id. No. 174, Seq. Id. No. 175, Seq. Id. No. 176, Seq. Id. No. 177, Seq. Id. No. 178, Seq. Id. No. 179, Seq. Id. No. 180, Seq. Id. No. 181, Seq. Id. No. 182, Seq. Id. No. 183, Seq. Id. No. 184, Seq. Id. No. 185, Seq. Id. No. 186, Seq. Id. No. 187, Seq. Id. No. 188, Seq. Id. No. 189, Seq. Id. No. 190, Seq. Id. No. 191, Seq. Id. No. 192, Seq. Id. No. 193, Seq. Id. No. 194, Seq. Id. No. 195, Seq. Id. No. 196, Seq. Id. No. 197, Seq. Id. No. 198, Seq. Id. No. 199, Seq. Id. No. 200, Seq. Id. No. 201, Seq. Id. No. 202, Seq. Id. No. 203, Seq. Id. No. 204, Seq. Id. No. 205, Seq. Id. No. 206, Seq. Id. No. 207, Seq. Id. No. 208, Seq. Id. No. 209, Seq. Id. No. 210, Seq. Id. No. 211, Seq. Id. No. 212, Seq. Id. No. 213, Seq. Id. No. 214, Seq. Id. No. 215, Seq. Id. No. 216, Seq. Id. No. 217, Seq. Id. No. 218, Seq. Id. No. 219, Seq. Id. No. 220, Seq. Id. No. 221, Seq. Id. No. 222, Seq. Id. No. 223, Seq. Id. No. 224, Seq. Id. No. 225, Seq. Id. No. 226, Seq. Id. No. 227, Seq. Id. No. 228, Seq. Id. No. 229, Seq. Id. No. 230, Seq. Id. No. 231, Seq. Id. No. 232, Seq. Id. No. 233, Seq. Id. No. 234, Seq. Id. No. 235, Seq. Id. No. 236, Seq. Id. No. 237, Seq. Id. No. 238, Seq. Id. No. 239, Seq. Id. No. 240, Seq. Id. No. 241, Seq. Id. No. 242, Seq. Id. No. 243, Seq. Id. No. 244, Seq. Id. No. 245, Seq. Id. No. 246, Seq. Id. No. 247, Seq. Id. No. 248, Seq. Id. No. 249, Seq. Id. No. 250, Seq. Id. No. 251, Seq. Id. No. 252, Seq. Id. No. 253, Seq. Id. No. 254, Seq. Id. No. 255, Seq. Id. No. 256, Seq. Id. No. 257, Seq. Id. No. 258, Seq. Id. No. 259, Seq. Id. No. 260, Seq. Id. No. 261, Seq. Id. No. 262, Seq. Id. No. 263, Seq. Id. No. 264, Seq. Id. No. 265, Seq. Id. No. 266, Seq. Id. No. 267, Seq. Id. No. 268, Seq. Id. No. 269, Seq. Id. No. 270, Seq. Id. No. 271, Seq. Id. No. 272, Seq. Id. No. 273, Seq. Id. No. 274, Seq. Id. No. 275, Seq. Id. No. 276, Seq. Id. No. 277, Seq. Id. No. 278, Seq. Id. No. 279, Seq. Id. No. 280, Seq. Id. No. 281, Seq. Id. No. 282, Seq. Id. No. 283, Seq. Id. No. 284, Seq. Id. No. 285, Seq. Id. No. 286, Seq. Id. No. 287, Seq. Id. No. 288, Seq. Id. No. 289, Seq. Id. No. 290, Seq. Id. No. 291, Seq. Id. No. 292, Seq. Id. No. 293, Seq. Id. No. 294, Seq. Id. No. 295, Seq. Id. No. 296, Seq. Id. No. 297, Seq. Id. No. 298, Seq. Id. No. 299, Seq. Id. No. 300, Seq. Id. No. 301, Seq. Id. No. 302, Seq. Id. No. 303, Seq. Id. No. 304, Seq. Id. No. 305, Seq. Id. No. 306, Seq. Id. No. 307, Seq. Id. No. 308, Seq. Id. No. 309, Seq. Id. No. 310, Seq. Id. No. 311, Seq. Id. No. 312, Seq. Id. No. 313, Seq. Id. No. 314, Seq. Id. No. 315, Seq. Id. No. 316, Seq. Id. No. 317, Seq. Id. No. 318, Seq. Id. No. 319, Seq. Id. No. 320, Seq. Id. No. 321, Seq. Id. No. 322, Seq. Id. No. 323, Seq. Id. No. 324, Seq. Id. No. 325, Seq. Id. No. 326, Seq. Id. No. 327, Seq. Id. No. 328, Seq. Id. No. 329, Seq. Id. No. 330, Seq. Id. No. 331, Seq. Id. No. 332, Seq. Id. No. 333, Seq. Id. No. 334, Seq. Id. No. 335, Seq. Id. No. 336, Seq. Id. No. 337, Seq. Id. No. 338, Seq. Id. No. 339, Seq. Id. No. 340, Seq. Id. No. 341, Seq. Id. No. 342, Seq. Id. No. 343, Seq. Id. No. 344, Seq. Id. No. 345, Seq. Id. No. 346, Seq. Id. No. 347, Seq. Id. No. 348, Seq. Id. No. 349, Seq. Id. No. 350, Seq. Id. No. 351, Seq. Id. No. 352, Seq. Id. No. 353, Seq. Id. No. 354, Seq. Id. No. 355, Seq. Id. No. 356, Seq. Id. No. 357, Seq. Id. No. 358, Seq. Id. No. 359, Seq. Id. No. 360, Seq. Id. No. 361, Seq. Id. No. 362, Seq. Id. No. 363, Seq. Id. No. 364, Seq. Id. No. 365, Seq. Id. No. 366, Seq. Id. No. 367, Seq. Id. No. 368, Seq. Id. No. 369, Seq. Id. No. 370, Seq. Id. No. 371, Seq. Id. No. 372, Seq. Id. No. 373, Seq. Id. No. 374, Seq. Id. No. 375, Seq. Id. No. 376, Seq. Id. No. 377, Seq. Id. No. 378, Seq. Id. No. 379, Seq. Id. No. 380, Seq. Id. No. 381, Seq. Id. No. 382, Seq. Id. No. 383, Seq. Id. No. 384, Seq. Id. No. 385, Seq. Id. No. 386, Seq. Id. No. 387, Seq. Id. No. 388, Seq. Id. No. 389, Seq. Id. No. 390, Seq. Id. No. 391, Seq. Id. No. 392, Seq. Id. No. 393, Seq. Id. No. 394, Seq. Id. No. 395, Seq. Id. No. 396, Seq. Id. No. 397, Seq. Id. No. 398, Seq. Id. No. 399, Seq. Id. No. 400, Seq. Id. No. 401, Seq. Id. No. 402, Seq. Id. No. 403, Seq. Id. No. 404, Seq. Id. No. 405, Seq. Id. No. 406, Seq. Id. No. 407, Seq. Id. No. 408, Seq. Id. No. 409, Seq. Id. No. 410, Seq. Id. No. 411, Seq. Id. No. 412, Seq. Id. No. 413, Seq. Id. No. 414, Seq. Id. No. 415, Seq. Id. No. 416, Seq. Id. No. 417, Seq. Id. No. 418, Seq. Id. No. 419, Seq. Id. No. 420, Seq. Id. No. 421, Seq. Id. No. 422, Seq. Id. No. 423, Seq. Id. No. 424, Seq. Id. No. 425, Seq. Id. No. 426, Seq. Id. No. 427, Seq. Id. No. 428, Seq. Id. No. 429, Seq. Id. No. 430, Seq. Id. No. 431, Seq. Id. No. 432, Seq. Id. No. 433, Seq. Id. No. 434, Seq. Id. No. 435, Seq. Id. No. 436, Seq. Id. No. 437, Seq. Id. No. 438, Seq. Id. No. 439, Seq. Id. No. 440, Seq. Id. No. 441, Seq. Id. No. 442, Seq. Id. No. 443, Seq. Id. No. 444, Seq. Id. No. 445, Seq. Id. No. 446, Seq. Id. No. 447, Seq. Id. No. 448, Seq. Id. No. 449, Seq. Id. No. 450, Seq. Id. No. 451, Seq. Id. No. 452, Seq. Id. No. 453, Seq. Id. No. 454, Seq. Id. No. 455, Seq. Id. No. 456, Seq. Id. No. 457, Seq. Id. No. 458, Seq. Id. No. 459, Seq. Id. No. 460, Seq. Id. No. 461, Seq. Id. No. 462, Seq. Id. No. 463, Seq. Id. No. 464, Seq. Id. No. 465, Seq. Id. No. 466, Seq. Id. No. 467, Seq. Id. No. 468, Seq. Id. No. 469, Seq. Id. No. 470, Seq. Id. No. 471, Seq. Id. No. 472, Seq. Id. No. 473, Seq. Id. No. 474, Seq. Id. No. 475, Seq. Id. No. 476, Seq. Id. No. 477, Seq. Id. No. 478, Seq. Id. No. 479, Seq. Id. No. 480, Seq. Id. No. 481, Seq. Id. No. 482, Seq. Id. No. 483, Seq. Id. No. 484, Seq. Id. No. 485, Seq. Id. No. 486, Seq. Id. No. 487, Seq. Id. No. 488, Seq. Id. No. 489, Seq. Id. No. 490, Seq. Id. No. 491, Seq. Id. No. 492, Seq. Id. No. 493, Seq. Id. No. 494, Seq. Id. No. 495, Seq. Id. No. 496, Seq. Id. No. 497, Seq. Id. No. 498, Seq. Id. No. 499, Seq. Id. No. 500, Seq. Id. No. 501, Seq. Id. No. 502, Seq. Id. No. 503, Seq. Id. No. 504, Seq. Id. No. 505, Seq. Id. No. 506, Seq. Id. No. 507, Seq. Id. No. 508, Seq. Id. No. 509, Seq. Id. No. 510, Seq. Id. No. 511, Seq. Id. No. 512, Seq. Id. No. 513, Seq. Id. No. 514, Seq. Id. No. 515, Seq. Id. No. 516, Seq. Id. No. 517, Seq. Id. No. 518, Seq. Id. No. 519, Seq. Id. No. 520, Seq. Id. No. 521, Seq. Id. No. 522, Seq. Id. No. 523, Seq. Id. No. 524, Seq. Id. No. 525, Seq. Id. No. 526, Seq. Id. No. 527, Seq. Id. No. 528, Seq. Id. No. 529, Seq. Id. No. 530, Seq. Id. No. 531, Seq. Id. No. 532, Seq. Id. No. 533, Seq. Id. No. 534, Seq. Id. No. 535, Seq. Id. No. 536, Seq. Id. No. 537, Seq. Id. No. 538, Seq. Id. No. 539, Seq. Id. No. 540, Seq. Id. No. 541, Seq. Id. No. 542, Seq. Id. No. 543, Seq. Id. No. 544, Seq. Id. No. 545, Seq. Id. No. 546, Seq. Id. No. 547, Seq. Id. No. 548, Seq. Id. No. 549, Seq. Id. No. 550, Seq. Id. No. 551, Seq. Id. No. 552, Seq. Id. No. 553, Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 556, Seq. Id. No. 557, Seq. Id. No. 558, Seq. Id. No. 559, Seq. Id. No. 560, Seq. Id. No. 561, Seq. Id. No. 562, Seq. Id. No. 563, Seq. Id. No. 564, Seq. Id. No. 565, Seq. Id. No. 566, Seq. Id. No. 567, Seq. Id. No. 568, Seq. Id. No. 569, Seq. Id. No. 570, Seq. Id. No. 571, Seq. Id. No. 572, Seq. Id. No. 573, Seq. Id. No. 574, Seq. Id. No. 575, Seq. Id. No. 576, Seq. Id. No. 577, Seq. Id. No. 578, Seq. Id. No. 579, Seq. Id. No. 580, Seq. Id. No. 581, Seq. Id. No. 582, Seq. Id. No. 583, Seq. Id. No. 584, Seq. Id. No. 585, Seq. Id. No. 586, Seq. Id. No. 587, Seq. Id. No. 588, Seq. Id. No. 589, Seq. Id. No. 590, Seq. Id. No. 591, Seq. Id. No. 592, Seq. Id. No. 593, Seq. Id. No. 594, Seq. Id. No. 595, Seq. Id. No. 596, Seq. Id. No. 597, Seq. Id. No. 598, Seq. Id. No. 599, Seq. Id. No. 600, Seq. Id. No. 601, Seq. Id. No. 602, Seq. Id. No. 603, Seq. Id. No. 604, Seq. Id. No. 605, Seq. Id. No. 606, Seq. Id. No. 607, Seq. Id. No. 608, Seq. Id. No. 609, Seq. Id. No. 610, Seq. Id. No. 611, Seq. Id. No. 612, Seq. Id. No. 613, Seq. Id. No. 614, Seq. Id. No. 615, Seq. Id. No. 616, Seq. Id. No. 617, Seq. Id. No. 618, and Seq. Id. No. 619.
20. The method according to any of claims 19, wherein the autoantibody recognizes an EGFR peptide that is selected from the group consisting of Seq. Id. No. 3, Seq. Id. No. 8, Seq. Id. No. 9, Seq. Id. No. 10, Seq. Id. No. 11, Seq. Id. No. 12, Seq. Id. No. 13, Seq. Id. No. 14, Seq. Id. No. 64, Seq. Id. No. 102, Seq. Id. No. 309, Seq. Id. No. 370, Seq. Id. No. 373, Seq. Id. No. 519, Seq. Id. No. 520, Seq. Id. No. 521, Seq. Id. No. 525, Seq. Id. No. 556, Seq. Id. No. 558, Seq. Id. No. 561, Seq. Id. No. 566, Seq. Id. No. 600, Seq. Id. No. 602 and Seq. Id. No. 603.
21. The method according to any of claims 17-20, wherein the level of an autoantibody in the blood sample of the human subject is 5 times higher than the level of said autoantibody representative for a human subject of a healthy population.
22. Erlotinib or a pharmaceutically acceptable salt thereof, in particular erlotinib hydrochloride, for use in treating a NSCLC patient identified by a method of any of claims 17 to 21 comprising administering erlotinib or a pharmaceutically acceptable salt thereof, in particular erlotinib hydrochloride to the patient.
23. Use of an autoantibody for predicting the response of a NSCLC patient to erlotinib or a pharmaceutically acceptable salt thereof, in particular erlotinib hydrochloride, treatment, which antibody was identified by a method of any of claims 17 to 21.
24. A kit for detecting in a blood sample of the human subject a level of one or more autoantibodies selected from the group of autoantibodies recognizing human EGFR, wherein an increased level of said autoantibodies selected from the group of autoantibodies recognizing human EGFR in the blood sample of the human subject compared to a level of said autoantibodies representative for a human subject of a healthy population is indicative for non-small cell lung cancer.
25. A kit according to claim 24, wherein the autoantibody recognizes an EGFR peptide that is selected from the group consisting of Seq. Id. No. 3, Seq. Id. No. 8, Seq. Id. No. 9, Seq. Id. No. 10, Seq. Id. No. 11, Seq. Id. No. 12, Seq. Id. No. 13, Seq. Id. No. 14, Seq. Id. No. 64, Seq. Id. No. 102, Seq. Id. No. 309, Seq. Id. No. 370, Seq. Id. No. 373, Seq. Id. No. 519, Seq. Id. No. 520, Seq. Id. No. 521, Seq. Id. No. 525, Seq. Id. No. 556, Seq. Id. No. 558, Seq. Id. No. 561, Seq. Id. No. 566, Seq. Id. No. 600, Seq. Id. No. 602 and Seq. Id. No. 603.
26. A kit according to claim 25, wherein the autoantibody recognizes an EGFR peptide that is selected from the group consisting of Seq. Id. No. 519, Seq. Id. No. 520, Seq. Id. No. 521, and Seq. Id. No. 561.
27. A method of diagnosis of non-small cell lung cancer in a human subject comprising: a) measuring in a blood sample of the human subject a level of an autoantibody selected from the group of autoantibodies recognizing mutated human EGFR,b) comparing the level of said autoantibody to a reference level, andc) providing a diagnosis of non-small cell lung cancer when the level of said autoantibody is above the reference level.
28. A method of diagnosis of non-small cell lung cancer in a human subject comprising: a) measuring in a blood sample of the human subject a level of an autoantibody selected from the group of autoantibodies recognizing mutated human EGFR,b) comparing the level of said autoantibody to a reference level, andc) recommending a treatment when the level of said autoantibody is above the reference level.
29. The method according to claim 27 or 28, wherein the autoantibody recognizes a mutated EGFR peptide is selected from the group consisting of Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 556, Seq. Id. No. 557, Seq. Id. No. 558, Seq. Id. No. 559, and Seq. Id. No. 560.
30. The method according to any of claims 28-29, wherein the autoantibody recognizes a mutated EGFR peptide is selected from the group consisting of Seq. Id. No. 1, Seq. Id. No. 2, Seq. Id. No. 4, Seq. Id. No. 5, Seq. Id. No. 6, Seq. Id. No. 7, Seq. Id. No. 15, Seq. Id. No. 16, Seq. Id. No. 17, Seq. Id. No. 18, Seq. Id. No. 19, Seq. Id. No. 20, Seq. Id. No. 21, Seq. Id. No. 22, Seq. Id. No. 23, Seq. Id. No. 24, Seq. Id. No. 25, Seq. Id. No. 26, Seq. Id. No. 27, Seq. Id. No. 28, Seq. Id. No. 29, Seq. Id. No. 30, Seq. Id. No. 31, Seq. Id. No. 32, Seq. Id. No. 33, Seq. Id. No. 34, Seq. Id. No. 35, Seq. Id. No. 36, Seq. Id. No. 37, Seq. Id. No. 38, Seq. Id. No. 39, Seq. Id. No. 40, Seq. Id. No. 41, Seq. Id. No. 42, Seq. Id. No. 43, Seq. Id. No. 44, Seq. Id. No. 45, Seq. Id. No. 46, Seq. Id. No. 47, Seq. Id. No. 48, Seq. Id. No. 49, Seq. Id. No. 50, Seq. Id. No. 51, Seq. Id. No. 52, Seq. Id. No. 53, Seq. Id. No. 54, Seq. Id. No. 55, Seq. Id. No. 56, Seq. Id. No. 57, Seq. Id. No. 58, Seq. Id. No. 59, Seq. Id. No. 60, Seq. Id. No. 61, Seq. Id. No. 62, Seq. Id. No. 63, Seq. Id. No. 65, Seq. Id. No. 66, Seq. Id. No. 67, Seq. Id. No. 68, Seq. Id. No. 69, Seq. Id. No. 70, Seq. Id. No. 71, Seq. Id. No. 72, Seq. Id. No. 73, Seq. Id. No. 74, Seq. Id. No. 75, Seq. Id. No. 76, Seq. Id. No. 77, Seq. Id. No. 78, Seq. Id. No. 79, Seq. Id. No. 80, Seq. Id. No. 81, Seq. Id. No. 82, Seq. Id. No. 83, Seq. Id. No. 84, Seq. Id. No. 85, Seq. Id. No. 86, Seq. Id. No. 87, Seq. Id. No. 88, Seq. Id. No. 89, Seq. Id. No. 90, Seq. Id. No. 91, Seq. Id. No. 92, Seq. Id. No. 93, Seq. Id. No. 94, Seq. Id. No. 95, Seq. Id. No. 96, Seq. Id. No. 97, Seq. Id. No. 98, Seq. Id. No. 99, Seq. Id. No. 100, Seq. Id. No. 101, Seq. Id. No. 103, Seq. Id. No. 104, Seq. Id. No. 105, Seq. Id. No. 106, Seq. Id. No. 107, Seq. Id. No. 108, Seq. Id. No. 109, Seq. Id. No. 110, Seq. Id. No. 111, Seq. Id. No. 112, Seq. Id. No. 113, Seq. Id. No. 114, Seq. Id. No. 115, Seq. Id. No. 116, Seq. Id. No. 117, Seq. Id. No. 118, Seq. Id. No. 119, Seq. Id. No. 120, Seq. Id. No. 121, Seq. Id. No. 122, Seq. Id. No. 123, Seq. Id. No. 124, Seq. Id. No. 125, Seq. Id. No. 126, Seq. Id. No. 127, Seq. Id. No. 128, Seq. Id. No. 129, Seq. Id. No. 130, Seq. Id. No. 131, Seq. Id. No. 132, Seq. Id. No. 133, Seq. Id. No. 134, Seq. Id. No. 135, Seq. Id. No. 136, Seq. Id. No. 137, Seq. Id. No. 138, Seq. Id. No. 139, Seq. Id. No. 140, Seq. Id. No. 141, Seq. Id. No. 142, Seq. Id. No. 143, Seq. Id. No. 144, Seq. Id. No. 145, Seq. Id. No. 146, Seq. Id. No. 147, Seq. Id. No. 148, Seq. Id. No. 149, Seq. Id. No. 150, Seq. Id. No. 151, Seq. Id. No. 152, Seq. Id. No. 153, Seq. Id. No. 154, Seq. Id. No. 155, Seq. Id. No. 156, Seq. Id. No. 157, Seq. Id. No. 158, Seq. Id. No. 159, Seq. Id. No. 160, Seq. Id. No. 161, Seq. Id. No. 162, Seq. Id. No. 163, Seq. Id. No. 164, Seq. Id. No. 165, Seq. Id. No. 166, Seq. Id. No. 167, Seq. Id. No. 168, Seq. Id. No. 169, Seq. Id. No. 170, Seq. Id. No. 171, Seq. Id. No. 172, Seq. Id. No. 173, Seq. Id. No. 174, Seq. Id. No. 175, Seq. Id. No. 176, Seq. Id. No. 177, Seq. Id. No. 178, Seq. Id. No. 179, Seq. Id. No. 180, Seq. Id. No. 181, Seq. Id. No. 182, Seq. Id. No. 183, Seq. Id. No. 184, Seq. Id. No. 185, Seq. Id. No. 186, Seq. Id. No. 187, Seq. Id. No. 188, Seq. Id. No. 189, Seq. Id. No. 190, Seq. Id. No. 191, Seq. Id. No. 192, Seq. Id. No. 193, Seq. Id. No. 194, Seq. Id. No. 195, Seq. Id. No. 196, Seq. Id. No. 197, Seq. Id. No. 198, Seq. Id. No. 199, Seq. Id. No. 200, Seq. Id. No. 201, Seq. Id. No. 202, Seq. Id. No. 203, Seq. Id. No. 204, Seq. Id. No. 205, Seq. Id. No. 206, Seq. Id. No. 207, Seq. Id. No. 208, Seq. Id. No. 209, Seq. Id. No. 210, Seq. Id. No. 211, Seq. Id. No. 212, Seq. Id. No. 213, Seq. Id. No. 214, Seq. Id. No. 215, Seq. Id. No. 216, Seq. Id. No. 217, Seq. Id. No. 218, Seq. Id. No. 219, Seq. Id. No. 220, Seq. Id. No. 221, Seq. Id. No. 222, Seq. Id. No. 223, Seq. Id. No. 224, Seq. Id. No. 225, Seq. Id. No. 226, Seq. Id. No. 227, Seq. Id. No. 228, Seq. Id. No. 229, Seq. Id. No. 230, Seq. Id. No. 231, Seq. Id. No. 232, Seq. Id. No. 233, Seq. Id. No. 234, Seq. Id. No. 235, Seq. Id. No. 236, Seq. Id. No. 237, Seq. Id. No. 238, Seq. Id. No. 239, Seq. Id. No. 240, Seq. Id. No. 241, Seq. Id. No. 242, Seq. Id. No. 243, Seq. Id. No. 244, Seq. Id. No. 245, Seq. Id. No. 246, Seq. Id. No. 247, Seq. Id. No. 248, Seq. Id. No. 249, Seq. Id. No. 250, Seq. Id. No. 251, Seq. Id. No. 252, Seq. Id. No. 253, Seq. Id. No. 254, Seq. Id. No. 255, Seq. Id. No. 256, Seq. Id. No. 257, Seq. Id. No. 258, Seq. Id. No. 259, Seq. Id. No. 260, Seq. Id. No. 261, Seq. Id. No. 262, Seq. Id. No. 263, Seq. Id. No. 264, Seq. Id. No. 265, Seq. Id. No. 266, Seq. Id. No. 267, Seq. Id. No. 268, Seq. Id. No. 269, Seq. Id. No. 270, Seq. Id. No. 271, Seq. Id. No. 272, Seq. Id. No. 273, Seq. Id. No. 274, Seq. Id. No. 275, Seq. Id. No. 276, Seq. Id. No. 277, Seq. Id. No. 278, Seq. Id. No. 279, Seq. Id. No. 280, Seq. Id. No. 281, Seq. Id. No. 282, Seq. Id. No. 283, Seq. Id. No. 284, Seq. Id. No. 285, Seq. Id. No. 286, Seq. Id. No. 287, Seq. Id. No. 288, Seq. Id. No. 289, Seq. Id. No. 290, Seq. Id. No. 291, Seq. Id. No. 292, Seq. Id. No. 293, Seq. Id. No. 294, Seq. Id. No. 295, Seq. Id. No. 296, Seq. Id. No. 297, Seq. Id. No. 298, Seq. Id. No. 299, Seq. Id. No. 300, Seq. Id. No. 301, Seq. Id. No. 302, Seq. Id. No. 303, Seq. Id. No. 304, Seq. Id. No. 305, Seq. Id. No. 306, Seq. Id. No. 307, Seq. Id. No. 308, Seq. Id. No. 310, Seq. Id. No. 311, Seq. Id. No. 312, Seq. Id. No. 313, Seq. Id. No. 314, Seq. Id. No. 315, Seq. Id. No. 316, Seq. Id. No. 317, Seq. Id. No. 318, Seq. Id. No. 319, Seq. Id. No. 320, Seq. Id. No. 321, Seq. Id. No. 322, Seq. Id. No. 323, Seq. Id. No. 324, Seq. Id. No. 325, Seq. Id. No. 326, Seq. Id. No. 327, Seq. Id. No. 328, Seq. Id. No. 329, Seq. Id. No. 330, Seq. Id. No. 331, Seq. Id. No. 332, Seq. Id. No. 333, Seq. Id. No. 334, Seq. Id. No. 335, Seq. Id. No. 336, Seq. Id. No. 337, Seq. Id. No. 338, Seq. Id. No. 339, Seq. Id. No. 340, Seq. Id. No. 341, Seq. Id. No. 342, Seq. Id. No. 343, Seq. Id. No. 344, Seq. Id. No. 345, Seq. Id. No. 346, Seq. Id. No. 347, Seq. Id. No. 348, Seq. Id. No. 349, Seq. Id. No. 350, Seq. Id. No. 351, Seq. Id. No. 352, Seq. Id. No. 353, Seq. Id. No. 354, Seq. Id. No. 355, Seq. Id. No. 356, Seq. Id. No. 357, Seq. Id. No. 358, Seq. Id. No. 359, Seq. Id. No. 360, Seq. Id. No. 361, Seq. Id. No. 362, Seq. Id. No. 363, Seq. Id. No. 364, Seq. Id. No. 365, Seq. Id. No. 366, Seq. Id. No. 367, Seq. Id. No. 368, Seq. Id. No. 369, Seq. Id. No. 371, Seq. Id. No. 372, Seq. Id. No. 374, Seq. Id. No. 375, Seq. Id. No. 376, Seq. Id. No. 377, Seq. Id. No. 378, Seq. Id. No. 379, Seq. Id. No. 380, Seq. Id. No. 381, Seq. Id. No. 382, Seq. Id. No. 383, Seq. Id. No. 384, Seq. Id. No. 385, Seq. Id. No. 386, Seq. Id. No. 387, Seq. Id. No. 388, Seq. Id. No. 389, Seq. Id. No. 390, Seq. Id. No. 391, Seq. Id. No. 392, Seq. Id. No. 393, Seq. Id. No. 394, Seq. Id. No. 395, Seq. Id. No. 396, Seq. Id. No. 397, Seq. Id. No. 398, Seq. Id. No. 399, Seq. Id. No. 400, Seq. Id. No. 401, Seq. Id. No. 402, Seq. Id. No. 403, Seq. Id. No. 404, Seq. Id. No. 405, Seq. Id. No. 406, Seq. Id. No. 407, Seq. Id. No. 408, Seq. Id. No. 409, Seq. Id. No. 410, Seq. Id. No. 411, Seq. Id. No. 412, Seq. Id. No. 413, Seq. Id. No. 414, Seq. Id. No. 415, Seq. Id. No. 416, Seq. Id. No. 417, Seq. Id. No. 418, Seq. Id. No. 419, Seq. Id. No. 420, Seq. Id. No. 421, Seq. Id. No. 422, Seq. Id. No. 423, Seq. Id. No. 424, Seq. Id. No. 425, Seq. Id. No. 426, Seq. Id. No. 427, Seq. Id. No. 428, Seq. Id. No. 429, Seq. Id. No. 430, Seq. Id. No. 431, Seq. Id. No. 432, Seq. Id. No. 433, Seq. Id. No. 434, Seq. Id. No. 435, Seq. Id. No. 436, Seq. Id. No. 437, Seq. Id. No. 438, Seq. Id. No. 439, Seq. Id. No. 440, Seq. Id. No. 441, Seq. Id. No. 442, Seq. Id. No. 443, Seq. Id. No. 444, Seq. Id. No. 445, Seq. Id. No. 446, Seq. Id. No. 447, Seq. Id. No. 448, Seq. Id. No. 449, Seq. Id. No. 450, Seq. Id. No. 451, Seq. Id. No. 452, Seq. Id. No. 453, Seq. Id. No. 454, Seq. Id. No. 455, Seq. Id. No. 456, Seq. Id. No. 457, Seq. Id. No. 458, Seq. Id. No. 459, Seq. Id. No. 460, Seq. Id. No. 461, Seq. Id. No. 462, Seq. Id. No. 463, Seq. Id. No. 464, Seq. Id. No. 465, Seq. Id. No. 466, Seq. Id. No. 467, Seq. Id. No. 468, Seq. Id. No. 469, Seq. Id. No. 470, Seq. Id. No. 471, Seq. Id. No. 472, Seq. Id. No. 473, Seq. Id. No. 474, Seq. Id. No. 475, Seq. Id. No. 476, Seq. Id. No. 477, Seq. Id. No. 478, Seq. Id. No. 479, Seq. Id. No. 480, Seq. Id. No. 481, Seq. Id. No. 482, Seq. Id. No. 483, Seq. Id. No. 484, Seq. Id. No. 485, Seq. Id. No. 486, Seq. Id. No. 487, Seq. Id. No. 488, Seq. Id. No. 489, Seq. Id. No. 490, Seq. Id. No. 491, Seq. Id. No. 492, Seq. Id. No. 493, Seq. Id. No. 494, Seq. Id. No. 495, Seq. Id. No. 496, Seq. Id. No. 497, Seq. Id. No. 498, Seq. Id. No. 499, Seq. Id. No. 500, Seq. Id. No. 501, Seq. Id. No. 502, Seq. Id. No. 503, Seq. Id. No. 504, Seq. Id. No. 505, Seq. Id. No. 506, Seq. Id. No. 507, Seq. Id. No. 508, Seq. Id. No. 509, Seq. Id. No. 510, Seq. Id. No. 511, Seq. Id. No. 512, Seq. Id. No. 513, Seq. Id. No. 514, Seq. Id. No. 515, Seq. Id. No. 516, Seq. Id. No. 517, Seq. Id. No. 518, Seq. Id. No. 522, Seq. Id. No. 523, Seq. Id. No. 524, Seq. Id. No. 526, Seq. Id. No. 527, Seq. Id. No. 528, Seq. Id. No. 529, Seq. Id. No. 530, Seq. Id. No. 531, Seq. Id. No. 532, Seq. Id. No. 533, Seq. Id. No. 534, Seq. Id. No. 535, Seq. Id. No. 536, Seq. Id. No. 537, Seq. Id. No. 538, Seq. Id. No. 539, Seq. Id. No. 540, Seq. Id. No. 541, Seq. Id. No. 542, Seq. Id. No. 543, Seq. Id. No. 544, Seq. Id. No. 545, Seq. Id. No. 546, Seq. Id. No. 547, Seq. Id. No. 548, Seq. Id. No. 549, Seq. Id. No. 550, Seq. Id. No. 551, Seq. Id. No. 552, Seq. Id. No. 553, Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 557, Seq. Id. No. 559, Seq. Id. No. 560, Seq. Id. No. 562, Seq. Id. No. 563, Seq. Id. No. 564, Seq. Id. No. 565, Seq. Id. No. 567, Seq. Id. No. 568, Seq. Id. No. 569, Seq. Id. No. 570, Seq. Id. No. 571, Seq. Id. No. 572, Seq. Id. No. 573, Seq. Id. No. 574, Seq. Id. No. 575, Seq. Id. No. 576, Seq. Id. No. 577, Seq. Id. No. 578, Seq. Id. No. 579, Seq. Id. No. 580, Seq. Id. No. 581, Seq. Id. No. 582, Seq. Id. No. 583, Seq. Id. No. 584, Seq. Id. No. 585, Seq. Id. No. 586, Seq. Id. No. 587, Seq. Id. No. 588, Seq. Id. No. 589, Seq. Id. No. 590, Seq. Id. No. 591, Seq. Id. No. 592, Seq. Id. No. 593, Seq. Id. No. 594, Seq. Id. No. 595, Seq. Id. No. 596, Seq. Id. No. 597, Seq. Id. No. 598, Seq. Id. No. 599, Seq. Id. No. 601, Seq. Id. No. 604, Seq. Id. No. 605, Seq. Id. No. 606, Seq. Id. No. 607, Seq. Id. No. 608, Seq. Id. No. 609, Seq. Id. No. 610, Seq. Id. No. 611, Seq. Id. No. 612, Seq. Id. No. 613, Seq. Id. No. 614, Seq. Id. No. 615, Seq. Id. No. 616, Seq. Id. No. 617, Seq. Id. No. 618 and Seq. Id. No. 619.
31. The method according to any of claims 27-30, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the groups consisting of Seq. Id. No. 1, Seq. Id. No. 2, Seq. Id. No. 4, Seq. Id. No. 5, Seq. Id. No. 6, Seq. Id. No. 7 and Seq. Id. No. 15.
32. The method according to any of claims 27-30, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 16, Seq. Id. No. 17, Seq. Id. No. 18, Seq. Id. No. 19, Seq. Id. No. 20, Seq. Id. No. 21, Seq. Id. No. 22, Seq. Id. No. 23, Seq. Id. No. 24, Seq. Id. No. 25, Seq. Id. No. 26, Seq. Id. No. 27, Seq. Id. No. 28, Seq. Id. No. 29, Seq. Id. No. 30, Seq. Id. No. 31, Seq. Id. No. 32, Seq. Id. No. 33, Seq. Id. No. 34, Seq. Id. No. 35, Seq. Id. No. 36, Seq. Id. No. 37, Seq. Id. No. 38, Seq. Id. No. 39, Seq. Id. No. 40, Seq. Id. No. 41, Seq. Id. No. 42, Seq. Id. No. 43, Seq. Id. No. 44, Seq. Id. No. 45, Seq. Id. No. 46, Seq. Id. No. 47, Seq. Id. No. 48, Seq. Id. No. 49, Seq. Id. No. 50, Seq. Id. No. 51, Seq. Id. No. 52, Seq. Id. No. 53, Seq. Id. No. 54, Seq. Id. No. 55, Seq. Id. No. 56, Seq. Id. No. 57, Seq. Id. No. 58, Seq. Id. No. 59, Seq. Id. No. 60, Seq. Id. No. 61, Seq. Id. No. 62, Seq. Id. No. 63, Seq. Id. No. 65, Seq. Id. No. 66, Seq. Id. No. 67, Seq. Id. No. 68, Seq. Id. No. 69, Seq. Id. No. 70, Seq. Id. No. 71, Seq. Id. No. 72, Seq. Id. No. 73, Seq. Id. No. 74, Seq. Id. No. 75, Seq. Id. No. 76, Seq. Id. No. 77, Seq. Id. No. 78, Seq. Id. No. 79, Seq. Id. No. 80, Seq. Id. No. 81, Seq. Id. No. 82, Seq. Id. No. 83, Seq. Id. No. 84, Seq. Id. No. 85, Seq. Id. No. 86, Seq. Id. No. 87, Seq. Id. No. 88, Seq. Id. No. 89, Seq. Id. No. 90, Seq. Id. No. 91, Seq. Id. No. 92, Seq. Id. No. 93, Seq. Id. No. 94, Seq. Id. No. 95, Seq. Id. No. 96, Seq. Id. No. 97, Seq. Id. No. 98, Seq. Id. No. 99, Seq. Id. No. 100, Seq. Id. No. 101, Seq. Id. No. 103, Seq. Id. No. 104, Seq. Id. No. 105, Seq. Id. No. 106, Seq. Id. No. 107, Seq. Id. No. 108, Seq. Id. No. 109, Seq. Id. No. 110, Seq. Id. No. 111, Seq. Id. No. 112, Seq. Id. No. 113, Seq. Id. No. 114, Seq. Id. No. 115, Seq. Id. No. 116, Seq. Id. No. 117, Seq. Id. No. 118, Seq. Id. No. 119, Seq. Id. No. 120, Seq. Id. No. 121, Seq. Id. No. 122, Seq. Id. No. 123, Seq. Id. No. 124, Seq. Id. No. 125, Seq. Id. No. 126, Seq. Id. No. 127, Seq. Id. No. 128, Seq. Id. No. 129, Seq. Id. No. 130, Seq. Id. No. 131, Seq. Id. No. 132, Seq. Id. No. 133, Seq. Id. No. 134, Seq. Id. No. 135, Seq. Id. No. 136, Seq. Id. No. 137, Seq. Id. No. 138, Seq. Id. No. 139, Seq. Id. No. 140, Seq. Id. No. 141, Seq. Id. No. 142, Seq. Id. No. 143, Seq. Id. No. 144, Seq. Id. No. 145, Seq. Id. No. 146, Seq. Id. No. 147, Seq. Id. No. 148, Seq. Id. No. 149, Seq. Id. No. 150, Seq. Id. No. 151, Seq. Id. No. 152, Seq. Id. No. 153, Seq. Id. No. 154, Seq. Id. No. 155, Seq. Id. No. 156, Seq. Id. No. 157, Seq. Id. No. 158, Seq. Id. No. 159, Seq. Id. No. 160, Seq. Id. No. 161, Seq. Id. No. 162, Seq. Id. No. 163, Seq. Id. No. 164, Seq. Id. No. 165, Seq. Id. No. 166, Seq. Id. No. 167, Seq. Id. No. 168, Seq. Id. No. 169, Seq. Id. No. 170, Seq. Id. No. 171, Seq. Id. No. 172, Seq. Id. No. 173, Seq. Id. No. 174, Seq. Id. No. 175, Seq. Id. No. 176, Seq. Id. No. 177, Seq. Id. No. 178, Seq. Id. 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No. 234, Seq. Id. No. 235, Seq. Id. No. 236, Seq. Id. No. 237, Seq. Id. No. 238, Seq. Id. No. 239, Seq. Id. No. 240, Seq. Id. No. 241, Seq. Id. No. 242, Seq. Id. No. 243, Seq. Id. No. 244, Seq. Id. No. 245, Seq. Id. No. 246, Seq. Id. No. 247, Seq. Id. No. 248, Seq. Id. No. 249, Seq. Id. No. 250, Seq. Id. No. 251, Seq. Id. No. 252, Seq. Id. No. 253, Seq. Id. No. 254, Seq. Id. No. 255, Seq. Id. No. 256, Seq. Id. No. 257, Seq. Id. No. 258, Seq. Id. No. 259, Seq. Id. No. 260, Seq. Id. No. 261, Seq. Id. No. 262, Seq. Id. No. 263, Seq. Id. No. 264, Seq. Id. No. 265, Seq. Id. No. 266, Seq. Id. No. 267, Seq. Id. No. 268, Seq. Id. No. 269, Seq. Id. No. 270, Seq. Id. No. 271, Seq. Id. No. 272, Seq. Id. No. 273, Seq. Id. No. 274, Seq. Id. No. 275, Seq. Id. No. 276, Seq. Id. No. 277, Seq. Id. No. 278, Seq. Id. No. 279, Seq. Id. No. 280, Seq. Id. No. 281, Seq. Id. No. 282, Seq. Id. No. 283, Seq. Id. No. 284, Seq. Id. No. 285, Seq. Id. No. 286, Seq. Id. No. 287, Seq. Id. No. 288, Seq. Id. 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No. 512, Seq. Id. No. 513, Seq. Id. No. 514, Seq. Id. No. 515, Seq. Id. No. 516 and Seq. Id. No. 517.
33. The method according to any of claims 27-30, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 518, Seq. Id. No. 522, Seq. Id. No. 523, Seq. Id. No. 524, Seq. Id. No. 526, Seq. Id. No. 527, Seq. Id. No. 528, Seq. Id. No. 529, Seq. Id. No. 530, Seq. Id. No. 531, Seq. Id. No. 532, Seq. Id. No. 533, Seq. Id. No. 534, Seq. Id. No. 535, Seq. Id. No. 536, Seq. Id. No. 537, Seq. Id. No. 538, Seq. Id. No. 539, Seq. Id. No. 540, Seq. Id. No. 541, Seq. Id. No. 542, Seq. Id. No. 543, Seq. Id. No. 544, Seq. Id. No. 545, Seq. Id. No. 546, Seq. Id. No. 547, Seq. Id. No. 548, Seq. Id. No. 549, Seq. Id. No. 550, Seq. Id. No. 551, Seq. Id. No. 552, Seq. Id. No. 553, Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 557, Seq. Id. No. 559, Seq. Id. No. 560, Seq. Id. No. 562, Seq. Id. No. 563, Seq. Id. No. 564, Seq. Id. No. 565, Seq. Id. No. 567, Seq. Id. No. 568, Seq. Id. No. 569, Seq. Id. No. 570, Seq. Id. No. 571, Seq. Id. No. 572, Seq. Id. No. 573, Seq. Id. No. 574, Seq. Id. No. 575, Seq. Id. No. 576, Seq. Id. No. 577, Seq. Id. No. 578, Seq. Id. No. 579, Seq. Id. No. 580, Seq. Id. No. 581, Seq. Id. No. 582, Seq. Id. No. 583, Seq. Id. No. 584, Seq. Id. No. 585, Seq. Id. No. 586, Seq. Id. No. 587, Seq. Id. No. 588, Seq. Id. No. 589, Seq. Id. No. 590, Seq. Id. No. 591, Seq. Id. No. 592, Seq. Id. No. 593, Seq. Id. No. 594, Seq. Id. No. 595, Seq. Id. No. 596, Seq. Id. No. 597, Seq. Id. No. 598, Seq. Id. No. 599 and Seq. Id. No. 601.
34. The method according to any of claims 27-30, wherein the autoantibody recognizes a mutated EGFR peptide that is selected from the group consisting of Seq. Id. No. 604, Seq. Id. No. 605, Seq. Id. No. 606, Seq. Id. No. 607, Seq. Id. No. 608, Seq. Id. No. 609, Seq. Id. No. 610, Seq. Id. No. 611, Seq. Id. No. 612, Seq. Id. No. 613, Seq. Id. No. 614, Seq. Id. No. 615, Seq. Id. No. 616, Seq. Id. No. 617, Seq. Id. No. 618 and Seq. Id. No. 619.
35. The method according to any of claims 27-34, wherein the level of an autoantibody in the blood sample of the human subject is 5 times higher than the level of said autoantibody representative for a human subject of a healthy population.
36. A method of diagnosis of non-small cell lung cancer in a human subject comprising: a) measuring in a blood sample of the human subject a level of an autoantibody selected from the group of autoantibodies recognizing human EGFR,b) comparing the level of said autoantibody to a reference level, andc) providing a diagnosis of non-small cell lung cancer when the level of said autoantibody is above the reference level.
37. A method of diagnosis of non-small cell lung cancer in a human subject comprising: a) measuring in a blood sample of the human subject a level of an autoantibody selected from the group of autoantibodies recognizing human EGFR,b) comparing the level of said autoantibody to a reference level, andc) recommending a treatment when the level of said autoantibody is above the reference level.
38. The method according to claim 36 or 37, wherein the autoantibody recognizes an EGFR peptide that is selected from the group consisting of Seq. Id. No. 3, Seq. Id. No. 8, Seq. Id. No. 9, Seq. Id. No. 10, Seq. Id. No. 11, Seq. Id. No. 12, Seq. Id. No. 13, Seq. Id. No. 14, Seq. Id. No. 64, Seq. Id. No. 102, Seq. Id. No. 309, Seq. Id. No. 370, Seq. Id. No. 373, Seq. Id. No. 519, Seq. Id. No. 520, Seq. Id. No. 521, Seq. Id. No. 525, Seq. Id. No. 556, Seq. Id. No. 558, Seq. Id. No. 561, Seq. Id. No. 566, Seq. Id. No. 600, Seq. Id. No. 602 and Seq. Id. No. 603.
39. The method according to any of claims 37-49, wherein the level of an autoantibody in the blood sample of the human subject is 5 times higher than the level of said autoantibody representative for a human subject of a healthy population.
40. The method according to any of claims 28-35, 37-39, wherein the treatment is erlotinib.

Priority Claims (1)

Number	Date	Country	Kind
12171126.1	Jun 2012	EP	regional

Autoimmune Antibodies

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Publication Number

Date Filed

Date Published

Inventors

CPC

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International Classifications

Abstract

Description

Claims

Priority Claims (1)