Compositions and methods for treating tumors presenting survivin antigens

• US 20070104689A1
• Filed: 09/26/2006
• Published: 05/10/2007
• Est. Priority Date: 09/27/2005
• Status: Abandoned Application

• Current Assignee: Merck Patent GmbH (Merck & Co., Inc.)
• Original Assignee: Merck Patent GmbH (Merck & Co., Inc.)
• Inventors: Hettmann, Thore, Gillies, Stephen, Stein, Pascal, Klinz, Stephan
• Application Number:
  US11/527,195
• Publication Number:
  US 20070104689A1
• Time in Patent Office: Days
• US Class Current: 424/93.200
• CPC Class Codes: A61K 2039/523 expressing foreign proteins
• CPC Class Codes: A61K 2039/5256 expressing foreign proteins
• CPC Class Codes: A61K 2039/5258 Virus-like particles
• CPC Class Codes: A61K 2039/53 DNA (RNA) vaccination
• CPC Class Codes: A61K 2039/55522 Cytokines; Lymphokines; Interferons
• CPC Class Codes: A61K 2039/55527 Interleukins
• CPC Class Codes: A61K 2239/55 Lung
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 39/00115 Apoptosis related proteins, e.g. survivin or livin
• CPC Class Codes: A61K 39/4611 T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
• CPC Class Codes: A61K 39/46445 Apoptosis related proteins, e.g. survivin or livin
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: C12N 2799/022 where the vector is derived from an adenovirus

Abstract

The present invention provides compositions and methods that elicit an immune response against diseased cells. In particular, the present invention provides compositions and methods for the presentation of a peptide related to survivin on antigen-presenting cells. Presentation of the peptide leads to an immune response in a mammal against cells such as tumor cells overexpressing survivin.

Claims

1. A vaccine comprising:

a nucleic acid encoding a peptide derived from a non-mammalian survivin;

or

a peptide derived from a non-mammalian survivin;

wherein the non-mammalian survivin comprises a BIR domain having more than 50%

amino acid identity but less than 90% amino acid identity with a human survivin BIR domain.

2. The vaccine of claim 1, comprising a nucleic acid encoding a peptide derived from a non-mammalian survivin.

3. The vaccine of claim 2, wherein the nucleic acid comprises a mammalian promoter.

4. The vaccine of claim 2, wherein the nucleic acid is a naked DNA.

5. The vaccine of claim 2, wherein the nucleic acid is formulated with a reagent that enhances transfection of mammalian cells.

6. The vaccine of claim 2, wherein the nucleic acid is part of a viral particle.

7. The vaccine of claim 6, wherein the viral particle is an adenoviral particle.

8. The vaccine of claim 2, wherein the vaccine comprises a bacterium comprising the nucleic acid.

9. The vaccine of claim 8, wherein the bacterium is an enteric bacterium.

10. The vaccine of claim 9, wherein the bacterium is a Salmonella.

11. The vaccine of claim 1, comprising a peptide derived from a non-mammalian survivin.

12. The vaccine of claim 1, wherein the peptide derived from a non-mammalian survivin comprises a BIR domain.

13. The vaccine of claim 1, wherein the BIR domain has more than 50% amino acid identity but less than 80% amino acid identity with a human survivin BIR domain.

14. The vaccine of claim 1, wherein the non-mammalian survivin is derived from a bird, fish, reptile, or amphibian.

15. The vaccine of claim 14, wherein the non-mammalian survivin is derived from a chicken.

16. The vaccine of claim 1, wherein the peptide derived from a non-mammalian survivin comprises a mutation that promotes T cell antigen presentation.

17. The vaccine of claim 16, wherein the mutation is an amino acid substitution at a position corresponding to Asn97, Thr99, Val100, or Gln101 of chicken survivin.

18. The vaccine of claim 17, wherein the mutation is one of the following:

N97E, T99M, V100L, or Q101G.

19. The vaccine of claim 1, wherein the vaccine is capable of activating T cells recognizing a human survivin peptide sequence when complexed with an MHC molecule.

20. The vaccine of claim 19, wherein the human survivin peptide sequence is selected from LTLGEFLKL, CPTENEPDL, and/or EPDLAQCFF.

21. The vaccine of claim 1, wherein the peptide derived from a non-mammalian survivin is biologically inert.

22. The vaccine of claim 1, wherein the peptide derived from a non-mammalian survivin comprises at least one amino acid substitution at a position corresponding to Arg18, Cys57, Cys60, His77, or Cys84 of human survivin.

23. The vaccine of claim 1, wherein the peptide derived from a non-mammalian survivin is fused to an Fc moiety.

24. The vaccine of claim 1, wherein the vaccine further encodes or includes a peptide derived from an effector molecule.

25. The vaccine of claim 24, wherein the effector molecule is a cytokine selected from the group consisting of IL-2, IL-7, IL-12, IL-18, IL-21, IL-23 and GM-CSF.

26. The vaccine of claim 1, further comprising an adjuvant.

50. A method of treatment comprising administering a vaccine of claim 1.

27. A vaccine comprising:

a nucleic acid encoding a modified mammalian survivin peptide;

or

a modified mammalian survivin peptide,

wherein the modified mammalian survivin peptide is biologically inert but immunologically substantially similar to mammalian survivin.

28. The vaccine of claim 27 comprising a nucleic acid encoding a modified mammalian survivin peptide.

29. The vaccine of claim 28, wherein the nucleic acid comprises a mammalian promoter.

30. The vaccine of claim 29, wherein the nucleic acid is a naked DNA.

31. The vaccine of claim 28, wherein the nucleic acid is formulated with a reagent that enhances transfection of mammalian cells.

32. The vaccine of claim 28, wherein the nucleic acid is part of a viral particle.

33. The vaccine of claim 32, wherein the viral particle is an adenoviral particle.

34. The vaccine of claim 28, wherein the vaccine comprises a bacterium comprising the nucleic acid.

35. The vaccine of claim 34, wherein the bacterium is an enteric bacterium.

36. The vaccine of claim 35, wherein the bacterium is a Salmonella.

37. The vaccine of claim 27 comprising a modified mammalian survivin peptide.

38. The vaccine of claim 27, wherein the modified mammalian survivin peptide comprises a modified BIR domain.

39. The vaccine of claim 38, wherein the modified BIR domain comprises at least one amino acid substitution at a position selected from the group consisting of Arg18, Cys57, Cys60, His77 and Cys84.

40. The vaccine of claim 27, wherein the modified mammalian survivin peptide comprises a modified helical domain.

41. The vaccine of claim 40, wherein the modified helical domain comprises at least one amino acid substitution at a position selected from the group consisting of Lys122, Ala128, and Ile135.

42. The vaccine of claim 41, wherein the modified helical domain comprises a Pro at position Ala128.

43. The vaccine of claim 41, wherein the modified helical domain comprises a Pro at position Ile135.

44. The vaccine of claim 27, wherein the modified mammalian survivin peptide comprises the amino acid sequence LTLGEFLKL or LMLGEFLKL.

45. The vaccine of claim 27, wherein the modified mammalian survivin peptide is fused to an Fc moiety.

46. The vaccine of claim 27, wherein the vaccine further encodes or includes a peptide derived from an effector molecule.

47. The vaccine of claim 46, wherein the effector molecule is a cytokine selected from the group consisting of IL-2, IL-7, IL-12, IL-18, IL-21, IL-23 and GM-CSF.

48. The vaccine of claim 27, further comprising an adjuvant.

51. A method of treatment comprising administering a vaccine of claim 27.

49. A nucleic acid capable of eliciting an immune response against cells expressing human survivin, wherein the nucleic acid encodes a peptide comprising an amino acid sequence with more than 50% identity but less than 80% identity with the human survivin BIR domain and wherein the nucleic acid comprises a promoter capable of expressing the peptide in a mammalian cell.

52. A method of treatment comprising administering a nucleic acid of claim 49.