Claims
- 1. A peptide of between 8 and about 20 amino acid residues in length, and including within its sequence the amino acid sequence of:
AA1—AA2—AA3—AA4—AA5—AA6—AA7—AA8; wherein AA1 is Leu or Ile; AA2 is Ala, Arg, Gln, Glu, Gly, Leu, Met, Phe, Pro, Ser, Thr, Tyr, or Val; AA3 is Ala, Gln, Glu, Gly, His, Lys, Met, Pro, Ser, Tyr, or Val; AA4 is Ala, Gln, Glu, Gly, Ile, Leu, Lys, Phe, Ser, Thr, Trp, Tyr, or Val; AA5 is Ala, Asn, Cys, Gln, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Thr, or Val; AA6 is Ala, Asn, Asp, Cys, Gln, Glu, Gly, Leu, Lys, Ser, or Thr; AA7 is Ala, Arg, Gln, Gly, His, Ile, Leu, Lys, Phe, Ser, Tyr, or Val; and AA8 is Val, Leu, Met, Gly, or Glu.
- 2. The peptide of claim 1, further defined as a peptide of between 8 and about 15 amino acid residues in length.
- 3. The peptide of claim 2, further defined as a peptide of between 8 and 10 amino acid residues in length.
- 4. The peptide of claim 3, further defined as having the amino acid sequence 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; or SEQ ID NO: 29.
- 5. The peptide of claim 4, further defined as having the amino acid sequence of SEQ ID NO: 1.
- 6. The peptide of claim 4, further defined as having the amino acid sequence of SEQ ID NO: 2.
- 7. The peptide of claim 4, further defined as having the amino acid sequence of SEQ ID NO: 3.
- 8. The peptide of claim 4, further defined as having the amino acid sequence of SEQ ID NO: 4.
- 9. The peptide of claim 4, further defined as having the amino acid sequence of SEQ ID NO: 5.
- 10. The peptide of claim 4, further defined as having the amino acid sequence of SEQ ID NO: 6.
- 11. The peptide of claim 4, further defined as having the amino acid sequence of SEQ ID NO: 7.
- 12. The peptide of claim 4, further defined as having the amino acid sequence of SEQ ID NO: 8.
- 13. The peptide of claim 4, further defined as having the amino acid sequence of SEQ ID NO: 9.
- 14. The peptide of claim 4, further defined as having the amino acid sequence of SEQ ID NO: 18.
- 15. The peptide of claim 4, further defined as having the amino acid sequence of SEQ ID NO: 19.
- 16. The peptide of claim 1, wherein
AA2 is Val or Gln; AA3 is Ser, Gln, Glu, Lys, or Pro; AA4 is Glu, Gly, Ile, Leu, or Ser; AA6 is Asn, Gln, or Ser; and AA7 is Arg, Leu, Gln, Tyr, Val, or Lys.
- 17. The peptide of claim 16, wherein
AA2 i s Val; AA3 is Ser; AA4 is Glu; AA6 is Ser; and AA7 is Arg or Lys.
- 18. A peptide of between 8 and about 20 amino acid residues in length, said peptide stimulating cytotoxic T-lymphocytes and comprising the amino acid sequence:
AA1—AA2—AA3—AA4—AA5—AA6—AA7—AA8; wherein
AA1 is Leu or Ile; AA2 is Ala, Arg, Gln, Glu, Gly, Leu, Met, Phe, Pro, Ser, Thr, Tyr, or Val; AA3 is Ala, Gln, Glu, Gly, His, Lys, Met, Pro, Ser, Tyr, or Val; AA4 is Ala, Gln, Glu, Gly, Ile, Leu, Lys, Phe, Ser, Thr, Trp, Tyr, or Val; AA5 is Ala, Asn, Cys, Gln, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Thr, or Val; AA6 is Ala, Asn, Asp, Cys, Gln, Glu, Gly, Leu, Lys, Ser, or Thr; AA7 is Ala, Arg, Gln, Gly, His, Ile, Leu, Lys, Phe, Ser, Tyr, or Val; and AA8 is Val, Leu, Met, Gly, or Glu.
- 19. The peptide of claim 18, further defined as being from 8 amino acid residues in length to about 15 amino acid residues in length.
- 20. The peptide of claim 19, further defined as being from 8 amino acid residues in length to about 10 amino acid residues in length.
- 21. The peptide of claim 20, further defined as being 8 amino acid residues in length.
- 22. The peptide of claim 21, further defined as being 9 amino acid residues in length.
- 23. The peptide of claim 21, further defined as being 10 amino acid residues in length.
- 24. The peptide of claim 18, further defined as having the amino acid sequence 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; or SEQ ID NO: 29.
- 25. The peptide of claim 24, further defined as having the amino acid sequence of SEQ ID NO: 1; SEQ ID NO: 2; SEQ ID NO: 3; SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 18, or SEQ ID NO: 19.
- 26. A peptide of between 8 and about 20 amino acid residues in length, said peptide binding HLA and stimulating cytotoxic T-lymphocytes, and including within its sequence an amino acid sequence represented by:
AA1—AA2—AA3—AA4—AA5—AA6—AA7—AA8; wherein
AA1 is Leu or Ile; AA2 is Ala, Arg, Gln, Glu, Gly, Leu, Met, Phe, Pro, Ser, Thr, Tyr, or Val; AA3 is Ala, Gln, Glu, Gly, His, Lys, Met, Pro, Ser, Tyr, or Val; AA4 is Ala, Gln, Glu, Gly, Ile, Leu, Lys, Phe, Ser, Thr, Trp, Tyr, or Val; AA5 is Ala, Asn, Cys, Gln, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Thr, or Val; AA6 is Ala, Asn, Asp, Cys, Gln, Glu, Gly, Leu, Lys, Ser, or Thr; AA7 is Ala, Arg, Gln, Gly, His, Ile, Leu, Lys, Phe, Ser, Tyr, or Val; and AA8 is Val, Leu, Met, Gly, or Glu.
- 27. The peptide of claim 26, wherein
AA2 is Val or Gln; AA3 is Ser, Gln, Glu, Lys, or Pro; AA4 is Glu, Gly, Ile, Leu, or Ser; AA6 is Asn, Gln, or Ser; and AA7 is Arg, Leu, Gln, Tyr, Val, or Lys.
- 28. The peptide of claim 27, wherein
AA2 is Val; AA3 is Ser; AA4 is Glu; AA6 is Ser; and AA7 is Arg or Lys.
- 29. The peptide of claim 26, further defined as having the amino acid sequence 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; or SEQ ID NO: 29.
- 30. A method for stimulating cytotoxic T-lymphocytes, comprising contacting said cytotoxic T-lymphocytes with an amount of a peptide in accordance with claim 1 effective to stimulate said cytotoxic T-lymphocytes.
- 31. The method of claim 30, wherein said cytotoxic T-lymphocytes are located within an animal and said peptide or composition is administered to said animal.
- 32. The method of claim 30, wherein said cytotoxic T-lymphocytes are obtained from an animal, contacted with said peptide, and re-administered to said animal.
- 33. The method of claim 30, wherein said peptide is formulated for administration parenterally, topically, or as an inhalant, aerosol or spray.
- 34. The method of claim 31, wherein said animal is a human subject.
- 35. A pharmaceutical composition including the composition of claim 1 in a pharmaceutically acceptable excipient.
- 36. The pharmaceutical composition of claim 35, wherein said composition comprises the peptide 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; or SEQ ID NO: 29.
- 37. A method of treating a proliferative cell disorder in an animal, comprising administering to said animal a therapeutically-effective amount of a pharmaceutical composition in accordance with claim 35.
- 38. The method of claim 37, wherein said proliferative cell disorder is cancer.
- 39. The method of claim 38, wherein said cancer is breast or ovarian cancer.
- 40. A method for detecting cytotoxic T-lymphocytes in a sample, comprising obtaining a sample suspected of containing cytotoxic T-lymphocytes, contacting said sample with a peptide in accordance with claim 1, under conditions effective to allow the formation of cell-peptide complexes, and detecting the cell-peptide complexes so formed.
- 41. The method of claim 40, wherein said sample is a biological sample from an animal suspected of having a HER-2/neu-related cancer.
- 42. The method of claim 40, wherein said peptide is linked to a detectable label and the cell-peptide complexes are detected by detecting the presence of the label.
- 43. The method of claim 40, wherein said cell-peptide complexes are detected by means of an antibody linked to a detectable label, the antibody having binding affinity for the peptide.
- 44. A method of generating an immune response, comprising administering to an animal a pharmaceutical composition comprising an immunologically effective amount of a composition comprising the peptide of claim 1.
- 45. The method of claim 44, wherein said composition comprises an immunologically effective amount of a composition comprising the peptide 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; or SEQ ID NO: 29.
- 46. A purified antibody that binds to the peptide of claim 1.
- 47. The antibody of claim 46, wherein the antibody is a monoclonal antibody.
- 48. The antibody of claim 46, wherein the antibody is linked to a detectable label.
- 49. The antibody of claim 48, wherein the antibody is linked to a radioactive label, a fluorogenic label, a nuclear magnetic spin resonance label, biotin or an enzyme that generates a colored product upon contact with a chromogenic substrate.
- 50. The antibody of claim 49, wherein the antibody is linked to an alkaline phosphatase, hydrogen peroxidase or glucose oxidase enzyme.
- 51. A method for detecting a neu-containing cancer cell, a neu protein, or neu peptide; the method comprising:
(a) generating an antibody that binds to the peptide of claim 1. (b) obtaining a sample suspected of containing a neu-containing cancer cell, a neu protein, or neu peptide; (c) contacting said sample with said antibody, under conditions effective to allow the formation of immune complexes; and (d) detecting the immune complexes so formed.
- 52. The method of claim 51, wherein said antibody is a monoclonal antibody.
- 53. An immunodetection kit comprising, in suitable container means, the peptide of claim 1, or a first antibody that binds to the peptide of claim 1, and an immunodetection reagent.
- 54. The immunodetection kit of claim 53, wherein the immunodetection reagent is a detectable label that is linked to said peptide or said first antibody.
- 55. The immunodetection kit of claim 54, wherein the immunodetection reagent is a detectable label that is linked to a second antibody that has binding affinity for said peptide or said first antibody.
- 56. The immunodetection kit of claim 54, wherein the immunodetection reagent is a detectable label that is linked to a second antibody that has binding affinity for a human antibody.
- 57. A DNA segment encoding the peptide of claim 1.
- 58. The DNA segment of claim 57, further defined as encoding the peptide of claim 3.
- 59. The DNA segment of claim 57, further defined as encoding the peptide of claim 4.
- 60. The DNA segment of claim 57, further defined as comprising the DNA sequence of 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; or SEQ ID NO: 64.
- 61. A recombinant vector comprising the DNA segment of claim 57.
- 62. The recombinant vector of claim 61, further defined as comprising a DNA segment encoding a peptide which stimulates a cytotoxic T-lymphocyte.
Government Interests
[0001] The United States government owns rights to the present invention pursuant to Grants CA 57293 and CA 16672 from the National Cancer Institute.
Continuations (1)
|
Number |
Date |
Country |
Parent |
08403459 |
Mar 1995 |
US |
Child |
10001546 |
Oct 2001 |
US |