Identification of MHC class I phospho-peptide antigens from breast cancer utilizing SHLA technology and complementary enrichment strategies

• US 10,640,535 B2
• Filed: 05/28/2013
• Issued: 05/05/2020
• Est. Priority Date: 05/25/2012
• Status: Active Grant

• Current Assignee: Agenus Inc.
• Original Assignee: Agenus Inc.
• Inventors: Hunt, Donald F., Norris, Andrew, English, Ann Michelle, Shabanowitz, Jeffrey, Hilderbrand, William H., Hawkins, Oriana E.
• Primary Examiner(s): Moseley, II, Nelson B
• Application Number:
  US14/403,350
• Publication Number:
  US 20150225456A1
• Time in Patent Office: 2,534 Days
• Field of Search: None
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 39/0011 Cancer antigens
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C07K 14/4748 Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/55 Fab or Fab'
• CPC Class Codes: C07K 7/06 having 5 to 11 amino acids
• CPC Class Codes: C07K 7/08 having 12 to 20 amino acids gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68

Abstract

The present invention describes novel tumor-specific phosphorylated peptides, nucleic acids encoding those peptides, and antibodies generated against said peptides. The genes, peptides, and antibodies described herein may be used as diagnostic indicators of the presence of breast cancer and/or used in therapeutics to treat breast cancer.

Claims

1. A composition comprising:

(a) an isolated or synthetic phosphopeptide having a length of 10 to 30 amino acids and comprising a sequence selected from the group consisting of;

SEQ ID NO;

132;

SEQ ID NO;

132 wherein the serine at the fourth position is phosphorylated;

SEQ ID NO;

71 wherein the serine at the fourth position is phosphorylated;

SEQ ID NO;

72 wherein the serine at the eighth position is phosphorylated;

SEQ ID NO;

73 wherein the serine at the sixth position is phosphorylated;

SEQ ID NO;

75 wherein the serine at the sixth position is phosphorylated;

SEQ ID NO;

76 wherein the serine at the eighth position is phosphorylated;

SEQ ID NO;

78 wherein the serine at the sixth position is phosphorylated;

SEQ ID NO;

79 wherein the serine at the fourth position is phosphorylated;

SEQ ID NO;

80 wherein the threonine at the third position is phosphorylated;

SEQ ID NO;

84 wherein the serine at the fourth position is phosphorylated;

SEQ ID NO;

87 wherein the serine at the eighth position is phosphorylated;

SEQ ID NO;

93 wherein the serine at the fourth position is phosphorylated;

SEQ ID NO;

94 wherein the serine at the fifth position is phosphorylated;

SEQ ID NO;

97 wherein the serine at the fourth position is phosphorylated;

SEQ ID NO;

99 wherein the serine at the sixth position is phosphorylated;

SEQ ID NO;

100 wherein the serine at the fourth position is phosphorylated;

SEQ ID NO;

101 wherein the serine at the sixth position is phosphorylated;

SEQ ID NO;

102 wherein the serine at the fourth position is phosphorylated;

SEQ ID NO;

104 wherein the serine at the sixth position is phosphorylated;

SEQ ID NO;

105 wherein the serine at the fourth position is phosphorylated;

SEQ ID NO;

110 wherein the serine at the fourth position is phosphorylated;

SEQ ID NO;

112 wherein the serine at the fourth position is phosphorylated;

SEQ ID NO;

113 wherein the serine at the fourth position is phosphorylated;

SEQ ID NO;

114 wherein the serine at the fourth position is phosphorylated;

SEQ ID NO;

115 wherein the serine at the fourth position is phosphorylated;

SEQ ID NO;

117 wherein the serine at the sixth position is phosphorylated;

SEQ ID NO;

118 wherein the serine at the tenth position is phosphorylated;

SEQ ID NO;

120 wherein the threonine at the fourth position is phosphorylated;

SEQ ID NO;

126 wherein the serine at the sixth position is phosphorylated;

SEQ ID NO;

127 wherein the serine at the sixth position is phosphorylated;

SEQ ID NO;

135 wherein the serine at the sixth position is phosphorylated;

SEQ ID NO;

140 wherein the serine at the fourth position is phosphorylated;

SEQ ID NO;

143 wherein the serine at the fourth position is phosphorylated;

SEQ ID NO;

145 wherein the serine at the fourth position is phosphorylated;

SEQ ID NO;

146 wherein the tyrosine at the fifth position is phosphorylated;

SEQ ID NO;

149 wherein the serine at the fourth position is phosphorylated;

SEQ ID NO;

151 wherein the serine at the eighth position is phosphorylated;

SEQ ID NO;

153 wherein the serine at the seventh position is phosphorylated;

SEQ ID NO;

154 wherein the serine at the fifth position is phosphorylated;

SEQ ID NO;

160 wherein the serine at the fourth position is phosphorylated;

SEQ ID NO;

161 wherein the serine at the fourth position is phosphorylated;

SEQ ID NO;

162 wherein the serine at the fourth position is phosphorylated and the serine at the eighth position is phosphorylated;

SEQ ID NO;

163 wherein the serine at the fourth position is phosphorylated;

SEQ ID NO;

166 wherein the serine at the seventh position is phosphorylated;

SEQ ID NO;

167 wherein the serine at the fourth position is phosphorylated;

SEQ ID NO;

168 wherein the serine at the fourth position is phosphorylated;

SEQ ID NO;

169 wherein the serine at the fourth position is phosphorylated;

SEQ ID NO;

170 wherein the serine at the seventh position is phosphorylated, and

(b) an adjuvant.

2. The composition of claim 1, wherein said composition has the ability to stimulate a T cell mediated immune response to at least one of said phosphopeptides.

3. The composition of claim 1, comprising a peptide capable of binding to the HLA-B*0702 allele on the MHC class I molecule.

4. A method of inducing an immunogenic response comprising administering to a patient in need thereof a therapeutically effective amount of the composition of claim 1.

5. A method of treating cancer comprising administering to a patient in need thereof a therapeutically effective amount of the composition of claim 1.

6. A method of treating breast cancer comprising administering to a patient in need thereof a therapeutically effective amount of the composition of claim 1.

7. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

132.

8. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

132, wherein the serine at the fourth position is phosphorylated.

9. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

71, wherein the serine at the fourth position is phosphorylated.

10. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

72, wherein the serine at the eighth position is phosphorylated.

11. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

73, wherein the serine at the sixth position is phosphorylated.

12. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

75, wherein the serine at the sixth position is phosphorylated.

13. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

76, wherein the serine at the eighth position is phosphorylated.

14. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

78, wherein the serine at the sixth position is phosphorylated.

15. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

79, wherein the serine at the fourth position is phosphorylated.

16. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

80, wherein the threonine at the third position is phosphorylated.

17. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

84, wherein the serine at the fourth position is phosphorylated.

18. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

87, wherein the serine at the eighth position is phosphorylated.

19. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

93, wherein the serine at the fourth position is phosphorylated.

20. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

94, wherein the serine at the fifth position is phosphorylated.

21. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

97, wherein the serine at the fourth position is phosphorylated.

22. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

99, wherein the serine at the sixth position is phosphorylated.

23. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

100, wherein the serine at the fourth position is phosphorylated.

24. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

101, wherein the serine at the sixth position is phosphorylated.

25. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

102, wherein the serine at the fourth position is phosphorylated.

26. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

104, wherein the serine at the sixth position is phosphorylated.

27. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

105, wherein the serine at the fourth position is phosphorylated.

28. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

110, wherein the serine at the fourth position is phosphorylated.

29. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

112, wherein the serine at the fourth position is phosphorylated.

30. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

113, wherein the serine at the fourth position is phosphorylated.

31. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

114, wherein the serine at the fourth position is phosphorylated.

32. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

115, wherein the serine at the fourth position is phosphorylated.

33. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

117, wherein the serine at the sixth position is phosphorylated.

34. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

118, wherein the serine at the tenth position is phosphorylated.

35. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

120, wherein the threonine at the fourth position is phosphorylated.

36. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

126, wherein the serine at the sixth position is phosphorylated.

37. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

127, wherein the serine at the sixth position is phosphorylated.

38. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

135, wherein the serine at the sixth position is phosphorylated.

39. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

140, wherein the serine at the fourth position is phosphorylated.

40. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

143, wherein the serine at the fourth position is phosphorylated.

41. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

145, wherein the serine at the fourth position is phosphorylated.

42. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

146, wherein the tyrosine at the fifth position is phosphorylated.

43. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

149, wherein the serine at the fourth position is phosphorylated.

44. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

151, wherein the serine at the eighth position is phosphorylated.

45. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

153, wherein the serine at the seventh position is phosphorylated.

46. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

154, wherein the serine at the fifth position is phosphorylated.

47. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

160, wherein the serine at the fourth position is phosphorylated.

48. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

161, wherein the serine at the fourth position is phosphorylated.

49. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

162, wherein the serine at the fourth position is phosphorylated and the serine at the eighth position is phosphorylated.

50. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

163, wherein the serine at the fourth position is phosphorylated.

51. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

166, wherein the serine at the seventh position is phosphorylated.

52. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

167, wherein the serine at the fourth position is phosphorylated.

53. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

168, wherein the serine at the fourth position is phosphorylated.

54. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

169, wherein the serine at the fourth position is phosphorylated.

55. The composition of claim 1, wherein the at least one synthetic target peptide comprises the amino acid sequence as set forth in SEQ ID NO:

170, wherein the serine at the seventh position is phosphorylated.