Methods for enhancing antigen-specific immune response using antibodies that bind OX-40
Compositions and methods for enhancing the immune response of a mammal to an antigen by engaging the OX-40 receptor on the surface of T-cells are disclosed, comprising administering to the mammal a composition comprising a purified antibody that specifically binds the OX-40 receptor and a pharmaceutically acceptable carrier, wherein said composition is administered to the mammal such that the antibody that specifically binds the OX-40 receptor is presented to T-cells of the mammal during or shortly after priming of the T-cells by the antigen. Such compositions and methods can be used in immunization and cancer treatment.
1. A method of enhancing an immune response of a mammal to an antigen expressed by a tumor cell, comprising
priming T cells in the mammal with the tumor antigen, wherein the priming comprises administering to the mammal a therapeutically effective amount of attenuated tumor cells, tumor cell membranes, or isolated tumor antigen; and
administering to the mammal a therapeutically effective amount of a composition consisting essentially of a purified antibody that specifically binds OX-40 polypeptide or an immunologically effective fragment of the antibody that specifically binds OX-40 polypeptide and a pharmaceutically acceptable carrier, wherein said composition is administered to the mammal such that the antibody that specifically binds OX-40 polypeptide or the immunologically effective fragment of the antibody is presented to T-cells of the mammal during or shortly after priming of the T-cells by the tumor antigen, thereby inducing the immune response, wherein the immune response is against the tumor cell.
2. A method according to claim 1 wherein the antibody that specifically binds OX-40 polypeptide or the immunologically effective fragment of the antibody that specifically binds OX-40 polypeptide is administered to the mammal about 3-7 days after administration of the antigen.
3. A method according to claim 1 wherein the antibody that specifically binds OX-40 polypeptide is a monoclonal antibody.
4. A method according to claim 3 wherein the monoclonal antibody is a humanized monoclonal antibody.
5. A method for stimulating the immune response of a mammal to a tumor cell in the mammal, comprising administering to the mammal a therapeutically effective dose of a solution consisting essentially of a purified antibody that specifically binds OX-40 polypeptide or an immunologically effective fragment of the antibody that specifically binds OX-40 polypeptide, and a composition comprising a tumor antigen, thereby stimulating the immune response of the mammal to the tumor cell.
6. A method according to claim 5 wherein the antibody that specifically binds OX-40 polypeptide is a monoclonal antibody.
7. A method according to claim 6 wherein the anti-OX-40 monoclonal antibody is a humanized monoclonal antibody.
8. A method of causing enhanced immune response against a tumor in a mammal, the method comprising:
priming T cells in the mammal with a tumor antigen expressed by the tumor, wherein the priming comprises administering to the mammal a therapeutically effective amount of an attenuated tumor cell, a tumor cell membrane, or an isolated tumor antigen;
increasing the amount of an antibody that specifically binds OX-40 polypeptide or an immunologically effective fragment of the antibody that specifically binds OX-40 polypeptide at the tumor site, wherein the antibody that specifically binds OX-40 polypeptide or an immunologically effective fragment of the antibody that specifically binds OX-40 polypeptide is administered in solution in a therapeutically effective amount, thereby causing enhanced immune response against the tumor.
9. The method of claim 8 wherein increasing the amount of the antibody that specifically binds the OX-40 polypeptide is achieved by administering to the tumor site a composition comprising antibody that specifically binds OX-40 polypeptide in solution and a carrier.
10. The method of claim 1 , wherein the antibody that specifically binds OX-40 polypeptide or the immunologically effective fragment of the antibody that specifically binds OX-40 polypeptide is in solution.
11. The method of claim 1 , wherein the antibody that specifically binds OX-40 polypeptide is presented to T-cells of the mammal during priming of the T-cells by the antigen.
12. The method of claim 1 , wherein the antibody that specifically binds OX-40 polypeptide is presented to T-cells of the mammal shortly after priming of the T-cells by the antigen.
13. The method of claim 1 , comprising administering to the mammal a composition consisting of a purified antibody that specifically binds OX-40 polypeptide or an immunologically effective fragment of the antibody that specifically binds OX-40 polypeptide and a pharmaceutically acceptable carrier, wherein said composition is administered to the mammal such that the antibody that specifically binds OX-40 polypeptide is presented to T-cells of the mammal during or shortly after priming of the T-cells by the antigen, thereby inducing the immune response, wherein the immune response is against a tumor cell.
14. The method of claim 5 , comprising administering to the mammal a therapeutically effective dose of a solution consisting of a purified antibody that specifically binds OX-40 polypeptide or an immunologically effective fragment of the antibody that specifically binds OX-40 polypeptide, thereby stimulating the immune response of the mammal to the tumor cell.
15. The method of claim 1 , wherein the priming comprises administering to the mammal a therapeutically effective amount of isolated tumor antigen.
16. The method of claim 15 , wherein the antibody that specifically binds OX-40 polypeptide and the isolated tumor antigen are administered as a single preparation.