Methods and compositions for modulating immune tolerance
The instant invention provides methods and compositions for modulation of the immune system. Specifically, the invention provides methods and compositions for increasing T cell mediated immune response useful in the treatment of cancer and chronic infection.
1. A pharmaceutical composition comprising a MC148-PE38 fusion molecule and a pharmaceutically acceptable carrier, wherein the MC148-PE38 fusion molecule comprises an amino acid sequence set forth in SEQ ID NO: 10.
2. The pharmaceutical composition of claim 1 , wherein the fusion molecule consists of an amino acid sequence set forth in SEQ ID NO: 10.
3. A method for increasing T cell mediated immune response in a subject comprising:
administering to the subject the pharmaceutical composition of claim 1 ;
thereby increasing the T cell mediated immune response.
4. The method of claim 3 , wherein the subject has a chronic infection.
5. The method of claim 4 , wherein the chronic infection is selected from the group consisting of HIV infection, HCV infection, HBV infection and TB infection.
6. The method of claim 3 , wherein the fusion molecule is administered to the location of a tumor.
7. A method of locally depleting T regulatory cells in a subject comprising:
locally administering to the subject the pharmaceutical composition of claim 1 ;
thereby depleting the T regulatory cells in the area of the administration of the fusion molecule.
8. The method of claim 7 , wherein the subject has a chronic infection.
9. The method of claim 8 , wherein the chronic infection is selected from the group consisting of HIV infection, HCV infection, HBV infection and TB infection.
10. The method of claim 7 , further comprising administering to the subject a vaccine near the location of the administration of the fusion molecule.
11. A method of inhibiting immune suppression in a subject comprising:
administering to the subject the pharmaceutical composition of claim 1 ;
thereby inhibiting immune suppression in the subject.
12. The method of claim 11 , wherein the subject has a chronic infection.
13. The method of claim 12 , wherein the chronic infection is selected from the group consisting of HIV infection, HCV infection, HBV infection and TB infection.
14. The method of claim 11 , wherein the fusion molecule is administered locally.
15. A method of modulating the suppressive effect of CD4+CD25+regulatory T cells of T effector cells in a subject comprising:
administering to the subject the pharmaceutical composition of claim 1 ;
thereby inhibiting immune suppression in the subject.
16. The method of claim 15 , wherein the subject has a chronic infection.
17. The method of claim 16 , wherein the chronic infection is selected from the group consisting of HIV infection, HCV infection, HBV infection and TB infection.
18. The method of claim 15 , wherein the subject is being administered a vaccine.
19. The method of claim 15 , wherein the fusion molecule is administered locally.
20. A method of modulating the suppressive state of T cells comprising:
administering to a subject an effective amount of the pharmaceutical composition of claim 1 ;
thereby inhibiting immune suppression in the subject.
21. A method of shifting an immune response from a Th2 response to a Th1 response in a subject comprising:
administering to the subject an effective amount of the pharmaceutical composition of claim 1 ; thereby killing Th2 cells and shifting the immune response.