IP Library Granted Patent US 7,378,096
Granted Patent B2
US 7,378,096 · App. 10/161,028 · Granted May 27, 2008

Stress protein compositions and methods for prevention and treatment of cancer and infectious disease

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Quick Facts
Patent No.
US 7,378,096
App. No.
10/161,028
Granted
May 27, 2008
Kind
B2
Abstract

Pharmaceutical compositions comprising a stress protein complex and related molecules encoding or cells presenting such a complex are provided. The stress protein complex comprises an hsp110 or grp170 polypeptide complexed with an immunogenic polypeptide. The immunogenic polypeptide of the stress protein complex can be associated with a cancer or an infectious disease. Preferred immunogenic polypeptides include gp100, her2/neu ECD-PD, ICD and M. tuberculosis antigens. The pharmaceutical compositions of the invention can be used for the treatment or prevention of cancer or infectious disease.

Claims (33)

1. A pharmaceutical composition comprising a stress protein complex and a physiologically acceptable carrier, wherein the stress protein complex comprises an hsp110 or grp170 polypeptide and an immunogenic polypeptide, wherein the immunogenic polypeptide has been denatured so as to enhance binding of the hsp110 or grp170 polypeptide to the immunogenic polypeptide.

2. The pharmaceutical composition of claim 1 , wherein the immunogenic polypeptide has been denatured by heating.

3. The pharmaceutical composition of claim 2 , wherein the heating comprises incubation at a temperature of at least 43° C.

4. The pharmaceutical composition of claim 1 , wherein the complex comprises a fusion protein.

5. The pharmaceutical composition of claim 1 , wherein the complex is derived from a tumor.

6. The pharmaceutical composition of claim 1 , wherein the complex is derived from a cell infected with an infectious agent.

7. The pharmaceutical composition of claim 1 , wherein the stress protein complex further comprises a polypeptide selected from the group consisting of members of the hsp70, hsp90, grp78 and grp94 stress protein families.

8. The pharmaceutical composition of claim 1 , wherein the stress protein complex comprises hsp110 complexed with hsp70 and hsp25.

9. The pharmaceutical composition of claim 1 , wherein the immunogenic polypeptide is associated with a cancer.

10. The pharmaceutical composition of claim 9 , wherein the immunogenic polypeptide comprises a her-2/neu peptide.

11. The pharmaceutical composition of claim 10 , wherein the her-2/neu peptide is derived from the extracellular domain of her-2/neu.

12. The pharmaceutical composition of claim 10 , wherein the her-2/neu peptide is derived from the intracellular domain of her-2/neu.

13. The pharmaceutical composition of claim 9 , wherein the immunogenic polypeptide comprises a gp100 peptide.

14. The pharmaceutical composition of claim 1 , wherein the immunogenic polypeptide is associated with an infectious disease.

15. The pharmaceutical composition of claim 14 , wherein the immunogenic polypeptide comprises a M. tuberculosis antigen.

16. The pharmaceutical composition of claim 15 , wherein the M. tuberculosis antigen is Mtb8.4 or Mtb39.

17. The pharmaceutical composition of claim 3 , wherein the incubation is about 30 minutes in duration.

18. The pharmaceutical composition of claim 1 , further comprising an adjuvant.

19. A method for producing T cells directed against a tumor cell comprising contacting a T cell with an antigen presenting cell (APC), wherein the APC is modified by contact with an hsp110 or grp170 polypeptide and an immunogenic polypeptide associated with the tumor cell, wherein the immunogenic polypeptide has been denatured so as to enhance binding of the hsp110 or grp170 polypeptide to the immunogenic polypeptide.

20. The method of claim 10 , wherein the T cell is a CD4+ or a CD8+ T cell.

21. A method for producing T cells directed against a M. tuberculosis -infected cell comprising contacting a T cell with an antigen presenting cell (APC), wherein the APC is modified by contact with an hsp110 or grp170 polypeptide and an immunogenic polypeptide associated with the M. tuberculosis -infected cell, wherein the immunogenic polypeptide has been denatured so as to enhance binding of the hsp110 or grp170 polypeptide to the immunogenic polypeptide.

22. The method of claim 21 , wherein the T cell is a CD4+ or a CD8+ T cell.

23. A method for reducing the severity of M. tuberculosis - infection in a subject, comprising administering to the subject an effective amount of the pharmaceutical composition of claim 15 , and thereby reducing the severity of M. tuberculosis - infection in the subject.

24. A method for inhibiting tumor growth in a subject having a tumor, comprising administering to the subject an effective amount of the pharmaceutical composition of claim 9 , thereby inhibiting tumor growth in said subject.

25. A method for inhibiting tumor growth in a subject having a precancerous condition, comprising administering to the subject an effective amount of a pharmaceutical composition comprising a stress protein complex and a physiological acceptable carrier, wherein the stress protein complex comprises an hsp110 or grp170 polypeptide, wherein the immunogenic polypeptide has been denatured so as to enhance binding of the hsp110 or grp170 polypeptide to the immunogenic polypeptide, and wherein the immunogenic polypeptide is associated with the precancerous condition.

26. A method of enhancing an immune response to an antigen administered to a subject comprising administering an hsp110 or grp170 polypeptide and the antigen to the subject, wherein the antigen has been heated so as to enhance binding of the hsp10 or grp170 polypeptide to the antigen.

27. A method of enhancing the immunogenicity of a stress protein complex comprising heating the stress protein complex, wherein the stress protein complex comprises an hsp110 or grp170 polypeptide and an immunogenic polypeptide associated with cancer or infectious disease, wherein the heating comprises incubating the stress protein complex at a temperature of at least 43° C.

28. The method of claim 26 , wherein the antigen has been heated by incubation at a temperature of at least 43° C.

29. The method of claim 28 , wherein the incubation is about 30 minutes in duration.

30. The method of claim 27 , wherein the incubating is about 30 minutes in duration.

31. The pharmaceutical composition of claim 9 , wherein the stress protein complex comprises hsp110 and gp100.

32. The pharmaceutical composition of claim 12 , wherein the stress protein complex comprises hsp110 and the intracellular domain of her-2/neu.

33. A method of enhancing the immunogenicity of a stress protein complex comprising heating the stress protein complex, wherein the stress protein complex comprises hsp110 and an immunogenic polypeptide associated with cancer or infectious disease.

Assignments (5)
CONFIRMATORY LICENSE Recorded Apr 23, 2010
From: ROSWELL PARK CANCER INSTITUTE
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 024283/0317 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 14, 2008
From: CORIXA CORPORATION DBA GLAXOSMITHKLINE BIOLOGICALS NORTH AMERICA
To: HEALTH RESEARCH, INC.
Reel/Frame 020794/0589 →
CORRECTIVE ASSIGNMENT TO CORRECT SPELLING OF FIRST NAMED INVENTOR AND FOURTH NAMED INVENTOR'S EXECUTION DATE REEL 013176/FRAME 0397 Recorded Nov 7, 2002
From: SUBJECK, JOHN R.; REPASKY, ELIZABETH A.; KAZIM, LATIF; WANG, XIANG-YANG; MANJILI, MASOUD H.
To: HEALTH RESEARCH, INC.
Reel/Frame 013875/0265 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 12, 2002
From: HENDERSON, ROBERT A.
To: CORIXA CORPORATION
Reel/Frame 013176/0365 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 12, 2002
From: SUBJECT, JOHN R.; REPASKY, ELIZABETH A.; KAZIM, LATIF; WANG, XIANG-YANG; MANJILI, MASOUD H.
To: HEALTH RESEARCH, INC.
Reel/Frame 013176/0397 →
Continuity (6)
Continuation In Part 0987218600 · Jun 1, 2001
Continuation In Part 0967634000 · Sep 29, 2000
Provisional Application 6021549700 · Jun 30, 2000
Provisional Application 6016313800 · Nov 2, 1999
Provisional Application 6015682100 · Sep 30, 1999
Related Publication 20080103095A1 · May 1, 2008