Claims
- 1. An isolated polypeptide, comprising at least an immunogenic portion of a breast tumor protein, wherein the tumor protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of:
(a) sequences recited in SEQ ID NOs: 2, 4-15, 18-33, 35-47, 49-56, 58, 59, 63-73, 88-116, 141-159, 175, 178, 180, 185, 186, 194, 199, 205, 208, 211, 214-216, 219, 222, 226, 232, 236, 240, 241, 245, 246, 252-268, 321-325, 343, 354, 367-369, 377, 382, 385, 389, 395, 397, 400, 408, 411, 413, 414, 416, 417, 419-423, 426, 427, 429, 431, 435-438, 441, 443-446, 450, 453, 454, 463-468, 474, 479, 484, 486 and 489; (b) sequences that hybridize to a sequence recited in any one of SEQ ID NOs: 2, 4-15, 18-33, 35-47, 49-56, 58, 59, 63-73, 88-116, 141-159, 175, 178, 180, 185, 186, 194, 199, 205, 208, 211, 214-216, 219, 222, 226, 232, 236, 240, 241, 245, 246, 252-268, 321-325, 343, 354, 367-369 377, 382, 385, 389, 395, 397, 400, 408, 411, 413, 414, 416, 417, 419-423, 426, 427, 429, 431, 435-438, 441, 443-446, 450, 453, 454, 463-468, 474, 479, 484, 486 and 489 under moderately stringent conditions; and (c) complements of sequences of (a) or (b).
- 2. An isolated polypeptide according to claim 1, wherein the polypeptide comprises an amino acid sequence that is encoded by a polynucleotide sequence recited in any one of SEQ ID NOs: 2, 4-15, 18-33, 35-47, 49-56, 58, 59, 63-73, 88-116, 141-159, 175, 178, 180, 185, 186, 194, 199, 205, 208, 211, 214-216, 219, 222, 226, 232, 236, 240, 241, 245, 246, 252-268, 321-325, 343, 354, 367-369, 377, 382, 385, 389, 395, 397, 400, 408, 411, 413, 414, 416, 417, 419-423, 426, 427, 429, 431, 435-438, 441, 443-446, 450, 453, 454, 463-468, 474, 479, 484, 486 and 489 or a complement of any of the foregoing polynucleotide sequences.
- 3. An isolated polypeptide comprising a sequence recited in any one of SEQ ID NOs:176, 179, 181, 469-473, 475, 485, 487 and 488.
- 4. An isolated polynucleotide encoding at least 15 amino acid residues of a breast tumor protein, or a variant thereof that differs in one or more substitutions, deletions, additions and/or insertions such that the ability of the variant to react with antigen-specific antisera is not substantially diminished, wherein the tumor protein comprises an amino acid sequence that is encoded by a polynucleotide comprising a sequence recited in any one of SEQ ID NOs:2, 4-15, 18-33, 35-47, 49-56, 58, 59, 63-73, 88-116, 141-159, 175, 178, 180, 185, 186, 194, 199, 205, 208, 211, 214-216, 219, 222, 226, 232, 236, 240, 241, 245, 246, 252-268, 321-325, 343, 354, 367-369, 377, 382, 385, 389, 395, 397, 400, 408, 411, 413, 414, 416, 417, 419-423, 426, 427, 429, 431, 435-438, 441, 443-446, 450, 453, 454, 463-468, 474, 479, 484 and 486 or a complement of any of the foregoing sequences.
- 5. An isolated polynucleotide encoding a breast tumor protein, or a variant thereof, wherein the tumor protein comprises an amino acid sequence that is encoded by a polynucleotide comprising a sequence recited in any one of SEQ ID NOs:2, 4-15, 18-33, 35-47, 49-56, 58, 59, 63-73, 88-116, 141-159, 175, 178, 180, 185, 186, 194, 199, 205, 208, 211, 214-216, 219, 222, 226, 232, 236, 240, 241, 245, 246, 252-268, 321-325, 343, 354, 367-369, 377, 382, 385, 389, 395, 397, 400, 408, 411, 413, 414, 416, 417, 419-423, 426, 427, 429, 431, 435-438, 441, 443-446, 450, 453, 454, 463-468, 474, 479, 484, 486 and 489 or a complement of any of the foregoing sequences.
- 6. An isolated polynucleotide, comprising a sequence recited in any one of SEQ ID NOs:2, 4-15, 18-33, 35-47, 49-56, 58, 59, 63-73, 88-116, 141-159, 175, 178, 180, 185, 186, 194, 199, 205, 208, 211, 214-216, 219, 222, 226, 232, 236, 240, 241, 245, 246, 252-268, 321-325, 343, 354, 367-369, 377, 382, 385, 389, 395, 397, 400, 408, 411, 413, 414, 416, 417, 419-423, 426, 427, 429, 431, 435-438, 441, 443-446, 450, 453, 454, 463-468, 474, 479, 484, 486 and 489.
- 7. An isolated polynucleotide, comprising a sequence that hybridizes to a sequence recited in any one of SEQ ID NOs: 2, 4-15, 18-33, 35-47, 49-56, 58, 59, 63-73, 88-116, 141-159, 175, 178, 180, 185, 186, 194, 199, 205, 208, 211, 214-216, 219, 222, 226, 232, 236, 240, 241, 245, 246, 252-268, 321-325, 343, 354, 367-369, 377, 382, 385, 389, 395, 397, 400, 408, 411, 413, 414, 416, 417, 419-423, 426, 427, 429, 431, 435-438, 441, 443-446, 450, 453, 454, 463-468, 474, 479, 484, 486 and 489 under moderately stringent conditions.
- 8. An isolated polynucleotide complementary to a polynucleotide according to any one of claims 4-7.
- 9. An expression vector, comprising a polynucleotide according to any one of claims 4-8.
- 10. A host cell transformed or transfected with an expression vector according to claim 9.
- 11. An isolated antibody, or antigen-binding fragment thereof, that specifically binds to a breast tumor protein that comprises an amino acid sequence that is encoded by a polynucleotide sequence recited in any one of SEQ ID NOs:2, 4-15, 18-33, 35-47, 49-56, 58, 59, 63-73, 88-116, 141-159, 175, 178, 180, 185, 186, 194, 199, 205, 208, 211, 214-216, 219, 222, 226, 232, 236, 240, 241, 245, 246, 252-268, 321-325, 343, 354, 367-369, 377, 382, 385, 389, 395, 397, 400, 408, 411, 413, 414, 416, 417, 419-423, 426, 427, 429, 431, 435-438, 441, 443-446, 450, 453, 454, 463-468, 474, 479, 484, 486 and 489 or a complement of any of the foregoing polynucleotide sequences.
- 12. A fusion protein, comprising at least one polypeptide according to claim 1.
- 13. A fusion protein according to claim 12, wherein the fusion protein comprises an expression enhancer that increases expression of the fusion protein in a host cell transfected with a polynucleotide encoding the fusion protein.
- 14. A fusion protein according to claim 12, wherein the fusion protein comprises a T helper epitope that is not present within the polypeptide of claim 1.
- 15. A fusion protein according to claim 12, wherein the fusion protein comprises an affinity tag.
- 16. An isolated polynucleotide encoding a fusion protein according to claim 12.
- 17. A pharmaceutical composition, comprising a physiologically acceptable carrier and at least one component selected from the group consisting of:
(a) a polypeptide according to claim 1;(b) a polynucleotide according to claim 4;(c) an antibody according to claim 11; (d) a fusion protein according to claim 12; and (e) a polynucleotide according to claim 16.
- 18. An immunogenic composition comprising an immunostimulant and at least one component selected from the group consisting of:
(a) a polypeptide according to claim 1;(b) a polynucleotide according to claim 4;(c) an antibody according to claim 11; (d) a fusion protein according to claim 12; and (e) a polynucleotide according to claim 16.
- 19. An immunogenic composition according to claim 18, wherein the immunostimulant is an adjuvant.
- 20. An immunogenic composition according to claim 18, wherein the immunostimulant induces a predominantly Type I response.
- 21. A method for inhibiting the development of a cancer in a patient, comprising administering to a patient an effective amount of a pharmaceutical composition according to claim 17.
- 22. A method for inhibiting the development of a cancer in a patient, comprising administering to a patient an effective amount of an immunogenic composition according to claim 18.
- 23. A pharmaceutical composition comprising an antigen-presenting cell that expresses a polypeptide according to claim 1, in combination with a pharmaceutically acceptable carrier or excipient.
- 24. A pharmaceutical composition according to claim 23, wherein the antigen presenting cell is a dendritic cell or a macrophage.
- 25. An immunogenic composition comprising an antigen-presenting cell that expresses a polypeptide comprising at least an immunogenic portion of a breast tumor protein, or a variant thereof, wherein the tumor protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of:
(a) sequences recited in SEQ ID NOs:1-175, 178, 180, 182-468, 474, 476, 477, 479, 484, 486 and 489 and 477; (b) sequences that hybridize to a sequence recited in any one of SEQ ID NOs: 1-175, 178, 180, 182-468, 474, 476, 477, 479, 484, 486 and 489 under moderately stringent conditions; and (c) complements of sequences of (i) or (ii); in combination with an immunostimulant.
- 26. An immunogenic composition according to claim 25, wherein the immunostimulant is an adjuvant.
- 27. An immunogenic composition according to claim 25, wherein the immunostimulant induces a predominantly Type I response.
- 28. An immunogenic composition according to claim 25, wherein the antigen-presenting cell is a dendritic cell.
- 29. A method for inhibiting the development of a cancer in a patient, comprising administering to a patient an effective amount of an antigen-presenting cell that expresses a polypeptide comprising at least an immunogenic portion of a breast tumor protein, or a variant thereof, wherein the tumor protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of:
(a) sequences recited in SEQ ID NOs: 1-175, 178, 180, 182-468, 474, 476, 477, 479, 484, 486 and 489; (b) sequences that hybridize to a sequence recited in any one of SEQ ID NOs: 1-175, 178, 180, 182-468, 474, 476 and 477 under moderately stringent conditions; and (c) complements of sequences of (i) or (ii)encoded by a polynucleotide recited in any one of SEQ ID NOs: 1-175, 178, 180, 182-468, 474, 476, 477, 479, 484, 486 and 489; and thereby inhibiting the development of a cancer in the patient.
- 30. A method according to claim 29, wherein the antigen-presenting cell is a dendritic cell.
- 31. A method according to any one of claims 21, 22 and 29, wherein the cancer is breast cancer.
- 32. A method for removing tumor cells from a biological sample, comprising contacting a biological sample with T cells that specifically react with a breast tumor protein, wherein the tumor protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of:
(i) polynucleotides recited in any one of SEQ ID NOs: 1-175, 178, 180, 182-468, 474, 476, 477, 479, 484, 486 and 489; and (ii) complements of the foregoing polynucleotides; wherein the step of contacting is performed under conditions and for a time sufficient to permit the removal of cells expressing the antigen from the sample.
- 33. A method according to claim 32, wherein the biological sample is blood or a fraction thereof.
- 34. A method for inhibiting the development of a cancer in a patient, comprising administering to a patient a biological sample treated according to the method of claim 32.
- 35. A method for stimulating and/or expanding T cells specific for a breast tumor protein, comprising contacting T cells with at least one component selected from the group consisting of:
(a) polypeptides comprising at least an immunogenic portion of a breast tumor protein, or a variant thereof, wherein the tumor protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of:
(i) sequences recited in SEQ ID NOs: 1-175, 178, 180, 182-468, 474, 476, 477, 479, 484, 486 and 489; (ii) sequences that hybridize to a sequence recited in any one of SEQ ID NOs: 1-175, 178, 180, 182-468, 474, 476, 477, 479, 484, 486 and 489 under moderately stringent conditions; and (iii) complements of sequences of (i) or (ii); (b) polynucleotides encoding a polypeptide of (a); and (c) antigen presenting cells that express a polypeptide of (a); under conditions and for a time sufficient to permit the stimulation and/or expansion of T cells.
- 36. An isolated T cell population, comprising T cells prepared according to the method of claim 35.
- 37. A method for inhibiting the development of a cancer in a patient, comprising administering to a patient an effective amount of a T cell population according to claim 36.
- 38. A method for inhibiting the development of a cancer in a patient, comprising the steps of:
(a) incubating CD4+ and/or CD8+ T cells isolated from a patient with at least one component selected from the group consisting of:
(i) polypeptides comprising at least an immunogenic portion of a breast tumor protein, or a variant thereof, wherein the tumor protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of:
(1) sequences recited in SEQ ID NOs:1-175, 178, 180, 182-468, 474, 476, 477, 479, 484, 486 and 489; (2) sequences that hybridize to a sequence recited in any one of SEQ ID NOs: 1-175, 178, 180, 182-468, 474, 476, 477, 479, 484, 486 and 489 under moderately stringent conditions; and (3) complements of sequences of (1) or (2); (ii) polynucleotides encoding a polypeptide of (i); and (iii) antigen presenting cells that expresses a polypeptide of (i); such that T cells proliferate; and (b) administering to the patient an effective amount of the proliferated T cells, and thereby inhibiting the development of a cancer in the patient.
- 39. A method for inhibiting the development of a cancer in a patient, comprising the steps of:
(a) incubating CD4+ and/or CD8+ T cells isolated from a patient with at least one component selected from the group consisting of:
(i) polypeptides comprising at least an immunogenic portion of a breast tumor protein, or a variant thereof, wherein the tumor protein comprises an amino acid sequence that is encoded by a polynucleotide sequence selected from the group consisting of:
(1) sequences recited in SEQ ID NOs: 1-175, 178, 180, 182-468, 474, 476, 477, 479, 484, 486 and 489; (2) sequences that hybridize to a sequence recited in any one of SEQ ID NOs:1-175, 178, 180, 182-468, 474, 476, 477, 479, 484, 486 and 489 under moderately stringent conditions; and (3) complements of sequences of (1) or (2); (ii) polynucleotides encoding a polypeptide of (i); and (iii) antigen presenting cells that express a polypeptide of (i); such that T cells proliferate;
(b) cloning at least one proliferated cell to provide cloned T cells; and (c) administering to the patient an effective amount of the cloned T cells, and thereby inhibiting the development of a cancer in the patient.
- 40. A method for determining the presence or absence of a cancer in a patient, comprising the steps of:
(a) contacting a biological sample obtained from a patient with a binding agent that binds to a breast tumor protein, wherein the tumor protein comprises an amino acid sequence that is encoded by a polynucleotide sequence recited in any one of SEQ ID NOs: 1-175, 178, 180, 182-468, 474, 476, 477, 479, 484, 486 and 489 or a complement of any of the foregoing polynucleotide sequences; (b) detecting in the sample an amount of polypeptide that binds to the binding agent; and (c) comparing the amount of polypeptide to a predetermined cut-off value, and therefrom determining the presence or absence of a cancer in the patient.
- 41. A method according to claim 40, wherein the binding agent is an antibody.
- 42. A method according to claim 43, wherein the antibody is a monoclonal antibody.
- 43. A method according to claim 40, wherein the cancer is breast cancer.
- 44. A method for monitoring the progression of a cancer in a patient, comprising the steps of:
(a) contacting a biological sample obtained from a patient at a first point in time with a binding agent that binds to a breast tumor protein, wherein the tumor protein comprises an amino acid sequence that is encoded by a polynucleotide sequence recited in any one of SEQ ID NOs:1-175, 178, 180, 182-468, 474, 476, 477, 479, 484, 486 and 489 or a complement of any of the foregoing polynucleotide sequences; (b) detecting in the sample an amount of polypeptide that binds to the binding agent; (c) repeating steps (a) and (b) using a biological sample obtained from the patient at a subsequent point in time; and (d) comparing the amount of polypeptide detected in step (c) to the amount detected in step (b) and therefrom monitoring the progression of the cancer in the patient.
- 45. A method according to claim 44, wherein the binding agent is an antibody.
- 46. A method according to claim 45, wherein the antibody is a monoclonal antibody.
- 47. A method according to claim 44, wherein the cancer is a breast cancer.
- 48. A method for determining the presence or absence of a cancer in a patient, comprising the steps of:
(a) contacting a biological sample obtained from a patient with an oligonucleotide that hybridizes to a polynucleotide that encodes a breast tumor protein, wherein the tumor protein comprises an amino acid sequence that is encoded by a polynucleotide sequence recited in any one of SEQ ID NO:1-175, 178, 180, 182-468, 474, 476, 477, 479, 484, 486 and 489 or a complement of any of the foregoing polynucleotide sequences; (b) detecting in the sample an amount of a polynucleotide that hybridizes to the oligonucleotide; and (c) comparing the amount of polynucleotide that hybridizes to the oligonucleotide to a predetermined cut-off value, and therefrom determining the presence or absence of a cancer in the patient.
- 49. A method according to claim 48, wherein the amount of polynucleotide that hybridizes to the oligonucleotide is determined using a polymerase chain reaction.
- 50. A method according to claim 48, wherein the amount of polynucleotide that hybridizes to the oligonucleotide is determined using a hybridization assay.
- 51. A method for monitoring the progression of a cancer in a patient, comprising the steps of:
(a) contacting a biological sample obtained from a patient with an oligonucleotide that hybridizes to a polynucleotide that encodes a breast tumor protein, wherein the tumor protein comprises an amino acid sequence that is encoded by a polynucleotide sequence recited in any one of SEQ ID NO:1-175, 178, 180, 182-468, 474, 476, 477, 479, 484, 486 and 489 or a complement of any of the foregoing polynucleotide sequences; (b) detecting in the sample an amount of a polynucleotide that hybridizes to the oligonucleotide; (c) repeating steps (a) and (b) using a biological sample obtained from the patient at a subsequent point in time; and (d) comparing the amount of polynucleotide detected in step (c) to the amount detected in step (b) and therefrom monitoring the progression of the cancer in the patient.
- 52. A method according to claim 51, wherein the amount of polynucleotide that hybridizes to the oligonucleotide is determined using a polymerase chain reaction.
- 53. A method according to claim 51, wherein the amount of polynucleotide that hybridizes to the oligonucleotide is determined using a hybridization assay.
- 54. A diagnostic kit, comprising:
(a) one or more antibodies according to claim 11; and (b) a detection reagent comprising a reporter group.
- 55. A kit according to claim 54, wherein the antibodies are immobilized on a solid support.
- 56. A kit according to claim 54, wherein the detection reagent comprises an anti-immunoglobulin, protein G, protein A or lectin.
- 57. A kit according to claim 54, wherein the reporter group is selected from the group consisting of radioisotopes, fluorescent groups, luminescent groups, enzymes, biotin and dye particles.
- 58. An oligonucleotide comprising 10 to 40 contiguous nucleotides that hybridize under moderately stringent conditions to a polynucleotide that encodes a breast tumor protein, wherein the tumor protein comprises an amino acid sequence that is encoded by a polynucleotide sequence recited in any one of SEQ ID NOs: 2, 4-15, 18-33, 35-47, 49-56, 58, 59, 63-73, 88-116, 141-159, 175, 178, 180, 185, 186, 194, 199, 205, 208, 211, 214-216, 219, 222, 226, 232, 236, 240, 241, 245, 246, 252-268, 321-325, 343, 354, 367-369, 377, 382, 385, 389, 395, 397, 400, 408, 411, 413, 414, 416, 417, 419-423, 426, 427, 429, 431, 435-438, 441, 443-446, 450, 453, 454, 463-468, 474, 479, 484, 486 and 489 or a complement of any of the foregoing polynucleotides.
- 59. A oligonucleotide according to claim 58, wherein the oligonucleotide comprises 10-40 contiguous nucleotides recited in any one of SEQ ID NOs: 2, 4-15, 18-33, 35-47, 49-56, 58, 59, 63-73, 88-116, 141-159, 175, 178, 180, 185, 186, 194, 199, 205, 208, 211, 214-216, 219, 222, 226, 232, 236, 240, 241, 245, 246, 252-268, 321-325, 343, 354, 367-369, 377, 382, 385, 389, 395, 397, 400, 408, 411, 413, 414, 416, 417, 419-423, 426, 427, 429, 431, 435-438, 441, 443-446, 450, 453, 454, 463-468, 474, 479, 484, 486 and 489.
- 60. A diagnostic kit, comprising:
(a) an oligonucleotide according to claim 59; and (b) a diagnostic reagent for use in a polymerase chain reaction or hybridization assay.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation-in-part of U.S. patent application Ser. No. 09/590,751, filed Jun. 8, 2000, which is a continuation-in-part of U.S. patent application Ser. No. 09/551,621, filed Apr. 17, 2000, which is a continuation-in-part of U.S. patent application Ser. No. 09/433,836, filed on Nov. 3, 1999, which is a continuation-in-part of U.S. application Ser. No. 09/389,681, filed on Sep. 2, 1999, which is a continuation-in-part of U.S. application Ser. No. 09/389,338, filed on Jun. 23, 1999, which is a continuation-in-part of U.S. application Ser. No. 09/285,480, filed on Apr. 2, 1999, which is a continuation-in-part of U.S. application Ser. No. 09/222,575, filed Dec. 28, 1998.
Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
09590751 |
Jun 2000 |
US |
Child |
09604287 |
Jun 2000 |
US |