Immune responses against HPV antigens elicited by compositions comprising an HPV antigen and a stress protein or an expression vector capable of expression of these proteins

• US 20030148456A1
• Filed: 11/07/2002
• Published: 08/07/2003
• Est. Priority Date: 08/05/1997
• Status: Active Grant

• Current Assignee: Nventa Biopharmaceuticals Corporation (Akela Pharma, Inc.)
• Original Assignee: Stressgen Biotechnologies Incorporated A British Columbia Canada Corporation
• Inventors: Chu, N. Randall, Mizzen, Lee A., Wu, Huacheng Bill
• Granted Patent: US 6,900,035 B2
• Time in Patent Office: Days
• US Class Current: 435/69.1
• CPC Class Codes: A61K 2039/51 comprising whole cells, viruses or DNA/RNA
• CPC Class Codes: A61K 2039/5156 expressing foreign proteins
• CPC Class Codes: A61K 2039/5256 expressing foreign proteins
• CPC Class Codes: A61K 2039/55516 Proteins; Peptides
• CPC Class Codes: A61K 2039/57 characterised by the type of response, e.g. Th1, Th2
• CPC Class Codes: A61K 2039/585 wherein the target is cancer
• CPC Class Codes: A61K 2039/60 characteristics by the carrier linked to the antigen
• CPC Class Codes: A61K 2039/6043 Heat shock proteins
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/385 Haptens or antigens, bound to carriers
• CPC Class Codes: A61K 47/646 the entire peptide or protein drug conjugate elicits an immune response, e.g. conjugate vaccines
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C07K 14/35 from Mycobacteriaceae (F)
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C12N 2710/20022 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2710/20034 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Abstract

The present invention relates to compositions for inducing an immune response, preferably a cellular, in particular a cell-mediated, cytolytic immune response, to human papillomavirus (HPV) protein antigens displayed by HPV or exhibited by infected cells including cells from cervical and other tumors. In one embodiment, compositions comprise an HPV protein antigen joined to a stress protein (or heat shock protein (Hsp)). The HPV protein antigen may be joined to the stress protein by chemical conjugation or noncovalently using linking moieties, or the HPV protein antigen and the stress protein may be joined in a fusion protein containing both HPV protein antigen and stress protein sequences. In another embodiment, compositions comprise an expression vector including, in expressible form, sequences encoding the HPV protein antigen and sequences encoding the stress protein. The expression vector can be introduced into cells of a subject, or it can be used to transduce cells of the subject ex vivo, resulting in the expression of an HPV protein antigen-stress protein fusion protein that will stimulate the subject'"'"'s immune response to the HPV protein antigen. The present invention also relates to compositions comprising a stress protein linked to an HPV antigen and another pharmacologically acceptable component, to stress protein-HPV protein antigen fusions and conjugates and to expression vectors encoding and capable of directing the expression in a subject'"'"'s cells of a fusion protein comprising a stress protein and an HPV protein antigen sequence. The present invention also relates to uses of these compositions to induce immune responses against HPV and HPV protein antigen-exhibiting cells including HPV-associated tumors.

Claims

1. A composition for inducing an immune response against an HPV protein antigen in a subject, the composition comprising an HPV protein antigen joined to a stress protein.

2. The composition of claim 1 wherein the immune response is a cellular immune response.

3. The composition of claim 1 wherein the stress protein is a mycobacterial stress protein.

4. The composition of claim 1 wherein the HPV protein antigen is the E6 or the E7 protein.

5. The composition of claim 1 wherein the stress protein is from the Hsp60 or the Hsp70 family.

6. A composition for inducing an immune response against an HPV protein antigen in a subject, the composition comprising an HPV protein antigen conjugated to a stress protein.

7. The composition of claim 6 wherein the immune response is a cellular immune response.

8. The composition of claim 6 wherein the stress protein is a mycobacterial stress protein.

9. The composition of claim 6 wherein the HPV protein antigen is the E6 or the E7 protein.

10. The composition of claim 6 wherein the stress protein is from the Hsp60 or the Hsp70 family.

11. A composition for inducing an immune response against an HPV protein antigen in a subject, the composition comprising a fusion protein comprising an HPV protein antigen fused to a stress protein.

12. The composition of claim 11 wherein the immune response is a cellular immune response.

13. The composition of claim 11 wherein the stress protein is a mycobacterial stress protein.

14. The composition of claim 11 wherein the HPV protein antigen is the E6 or the E7 protein.

15. The composition of claim 11 wherein the stress protein is from the Hsp60 or the Hsp70 family.

16. A composition comprising an HPV protein antigen joined to a stress protein in combination with another pharmacologically acceptable component.

17. The composition of claim 16 wherein the stress protein is a mycobacterial stress protein.

18. The composition of claim 16 wherein the HPV protein antigen is the E6 or the E7 protein.

19. The composition of claim 16 wherein the stress protein is from the Hsp60 or the Hsp70 family.

37. A method of inducing an immune response against an HPV protein antigen, comprising administering to a subject an effective amount of the composition of claim 16.

42. A method of treating a tumor expressing an HPV protein antigen, comprising administering to a subject an effective amount of the composition of claim 16.

20. A conjugate comprising an HPV protein antigen conjugated to a stress protein.

21. The conjugate of claim 20 wherein the stress protein is a mycobacterial stress protein.

22. The conjugate of claim 20 wherein the HPV protein antigen is the E6 or the E7 protein.

23. The conjugate of claim 20 wherein the stress protein is from the Hsp60 or the Hsp70 family.

38. A method of inducing an immune response against an HPV protein antigen, comprising administering to a subject an effective amount of the conjugate of claim 20.

43. A method of treating a tumor expressing an HPV protein antigen, comprising administering to a subject an effective amount of the conjugate of claim 20.

24. A fusion protein comprising an HPV protein antigen fused to a stress protein.

25. The fusion protein of claim 24 wherein the stress protein is a mycobacterial stress protein.

26. The fusion protein of claim 24 wherein the HPV protein antigen is the E6 or the E7 protein.

27. The fusion protein of claim 24 wherein the stress protein is from the Hsp60 or the Hsp70 family.

28. The fusion protein of claim 24 wherein the HPV protein antigen is E6 or E7 and the stress protein is from the Hsp60 or the Hsp70 family.

29. A composition for inducing an immune response against an HPV protein antigen in a subject, the composition comprising an expression vector encoding and capable of directing expression of the fusion protein of claim 24 in cells of the subject.

30. The composition of claim 29 wherein the immune response is a cellular immune response.

31. A composition for inducing an immune response against an HPV protein antigen in a subject, the composition comprising an expression vector encoding and capable of directing expression of the fusion protein of claim 28 in cells of the subject.

32. The composition of claim 31 wherein the immune response is a cellular immune response.

33. An expression vector encoding and capable of directing expression of the fusion protein of claim 24 in cells of a subject.

34. An expression vector encoding and capable of directing expression of the fusion protein of claim 28 in cells of a subject.

35. A method of inducing an immune response against an HPV protein antigen, comprising administering to a subject an effective amount of the expression vector of claim 33.

36. A method of inducing an immune response against an HPV protein antigen, comprising administering to a subject an effective amount of the expression vector of claim 34.

39. A method of inducing an immune response against an HPV protein antigen, comprising administering to a subject an effective amount of the fusion protein of claim 24.

40. A method of treating a tumor exhibiting an HPV protein antigen, comprising administering to a subject an effective amount of the expression vector of claim 33.

41. A method of treating a tumor exhibiting an HPV protein antigen, comprising administering to a subject an effective amount of the expression vector of claim 34.

44. A method of treating a tumor expressing an HPV protein antigen, comprising administering to a subject an effective amount of the fusion protein of claim 24.