Monoclonal antibodies to interleukin 35 and methods of use thereof to inhibit regulatory T cell function
Methods for regulating T cell function in a subject, particularly regulatory T cell activity are provided. Methods of the invention include administering to a subject a therapeutically effective amount of an Interleukin 35-specific binding agent, such as an antibody or small molecule inhibitor. The invention further provides methods for enhancing the immunogenicity of a vaccine or overcoming a suppressed immune response to a vaccine in a subject, including administering to the subject a therapeutically effective amount of an IL35-specific binding agent and administering to the subject a vaccine. In one embodiment the vaccine is a cancer vaccine.
1. A pharmaceutical composition comprising an excipient and an isolated human or humanized monoclonal antibody or antigen-binding fragment thereof capable of binding human Interleukin 35 (IL35) heterodimer, wherein the antibody is present in the composition in an amount effective to inhibit a regulatory T- cell function in a human subject to whom the composition is administered.
2. The pharmaceutical composition of claim 1 , wherein the monoclonal antibody specifically binds to the Epstein-Barr-virus-induced gene 3 (EBI3) subunit of IL35.
3. The pharmaceutical composition of claim 1 , wherein the monoclonal antibody specifically binds to the p35 subunit of IL35.
4. The pharmaceutical composition of claim 1 , wherein the monoclonal antibody does not specifically bind to Interleukin 12 (IL12).
5. The pharmaceutical composition of claim 1 , wherein the monoclonal antibody specifically binds to the EBI3 subunit of IL35 and specifically blocks IL35 regulatory T-cell activity.
6. The pharmaceutical composition of claim 1 , wherein the monoclonal antibody specifically binds to the p35 subunit of IL35 and specifically blocks IL35 regulatory T-cell activity.
7. The pharmaceutical composition of claim 1 , wherein the monoclonal antibody specifically interferes with IL35 formation or activity.
8. The pharmaceutical composition of claim 1 , wherein the monoclonal antibody is present in the composition in an amount effective to inhibit IL35 immunoregulatory activity.
9. The pharmaceutical composition of claim 1 , wherein the monoclonal antibody is present in the composition in an amount effective to reduce and/or block of one or more of the suppressive effects mediated by regulatory T-cells.
10. The pharmaceutical composition of claim 1 , wherein the monoclonal antibody is present in the composition in an amount effective to inhibit the activation and/or proliferation of regulatory T-cells relative to the activation and/or proliferation of effector T-cells.
11. The pharmaceutical composition of claim 1 , wherein the monoclonal antibody is present in the composition in an amount effective to prevent or overcome induction of tumor antigen tolerance by regulatory T-cells in a subject.
12. The pharmaceutical composition of claim 1 , wherein the monoclonal antibody is monovalent, bivalent, or a single-chain antibody.
13. The pharmaceutical composition of claim 1 , wherein the monoclonal antibody is present in the composition in an amount from about 0.1 to about 200 mg/kg body weight in single or divided doses.
14. A monoclonal antibody that specifically binds to human IL35.
15. The pharmaceutical composition of claim 1 , wherein the monoclonal antibody does not specifically bind to Interleukin 27 (IL27).
16. The monoclonal antibody of claim 14 , wherein the antibody is humanized or is a fully human antibody.
17. The monoclonal antibody of claim 14 , wherein the antibody is an antigen-binding fragment of the full-size monoclonal antibody .
18. The monoclonal antibody of claim 17 , wherein the fragment comprises a Fab.
19. The pharmaceutical composition of claim 1 , wherein the monoclonal antibody specifically interferes with IL35 formation.
20. The pharmaceutical composition of claim 1 , wherein the monoclonal antibody specifically interferes with IL35 activity.
21. The pharmaceutical composition of claim 1 , wherein the monoclonal antibody specifically competes with binding of an IL35 subunit.
22. A method of inhibiting a regulatory T-cell function in a subject, comprising administering to a subject in need of inhibiting a regulatory T-cell function a therapeutically effective amount of the pharmaceutical composition of claim 1 , wherein the therapeutically effective amount of said antibody inhibits a regulatory T-cell function in said subject.
23. A method of inhibiting a regulatory T cell function in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the antibody of claim 15 .