Therapeutic compositions that produce an immune response
View Patent ↗The invention provides a method for stimulating the production of antibodies to a cryptic epitope on a soluble antigen by administering to a patient having such a cryptic epitope a binding agent that binds to the soluble antigen and forming a complex between the binding agent and the soluble antigen, wherein the cryptic epitope is exposed and the patient generates antibodies that bind to the cryptic epitope.
1. A method of treating an oncological disease comprising stimulating a multi-epitopic immune response to a tumor-associated antigen comprising:
administering to a host a complex formed from a soluble tumor-associated antigen and an antibody or antigen binding fragment thereof that binds to a first epitope of the tumor-associated antigen, wherein the tumor-associated antigen is CA 125, and wherein the administration of the complex induces host antibodies reactive with at least one other epitope of the tumor-associated antigen.
2. The method of claim 1 , wherein the antibody is selected from the group consisting of a monoclonal antibody, a single chain antibody, a humanized antibody, and a chimeric antibody.
3. The method of claim 1 , wherein the host is a human.
4. The method of claim 1 , wherein the complex is administered with an adjuvant.
5. The method of claim 1 , wherein the antibody or antigen binding fragment thereof of the complex is formulated at a dose of from about 0.1 μg to about 2 mg per kilogram of body weight of the host.
6. The method of claim 1 , wherein the complex induces cytotoxic T cells reactive with the antigen.
7. The method of claim 1 , wherein the antibody or antigen binding fragment thereof is formulated in the complex at a dose of about 2 mg per host.
8. The method of claim 1 , wherein the antibody or antigen binding fragment thereof is formulated in the complex at a dose of from about 0.1 μg to about 200 μg per kilogram of body weight of the host.
9. The method of claim 1 , wherein the antibody is produced by the hybridoma having ATCC deposit number PTA-1883.
10. A method of treating an oncological disease comprising stimulating a multi-epitopic immune response to a tumor-associated antigen comprising administering to a host a complex consisting essentially of a soluble tumor-associated antigen and an antibody or antigen binding fragment thereof that binds to a first epitope of the tumor-associated antigen, wherein said tumor-associated antigen is CA 125, and wherein the administration of the complex induces host antibodies and cytotoxic T cells reactive with the tumor-associated antigen.
11. The method of claim 10 , wherein the antibody is produced by the hybridoma having ATCC deposit number PTA-1883.
12. A method of treating an oncological disease comprising stimulating a multi-epitopic immune response to a tumor-associated antigen comprising administering to a host a complex consisting essentially of a soluble tumor-associated antigen and an antibody or antigen binding fragment thereof that binds to a first epitope of the tumor-associated antigen, wherein said tumor-associated antigen is CA 125, and wherein the administration of the complex induces cytotoxic T cells reactive with the tumor-associated antigen.
13. The method of claim 12 , wherein the complex further induces host antibodies reactive with at least one other epitope of the tumor-associated antigen.
14. The method of claim 12 , wherein the antibody is produced by the hybridoma having ATCC deposit number PTA-1883.
15. A method of treating an oncological disease comprising administering to a host a complex formed from a soluble tumor-associated antigen and an antibody or antigen binding fragment thereof that binds to a first epitope of the tumor-associated antigen, wherein said tumor-associated antigen is CA 125, and wherein the administration of the complex induces host antibodies reactive with at least one other epitope of the tumor-associated antigen.
16. The method of claim 15 , wherein the complex induces cytotoxic T cells reactive with the tumor-associated antigen.
17. The method of claim 15 , wherein the complex induces host antibodies reactive with at least one other epitope of the antigen.
18. A method of treating an oncological disease comprising administering to a host a complex formed from a soluble tumor-associated antigen and an antibody or antigen binding fragment thereof that binds to a first epitope of the tumor-associated antigen, wherein said tumor-associated antigen is CA 125, and wherein the administration of the complex induces cytotoxic T cells reactive with the tumor-associated antigen.
19. A method of treating an oncological disease comprising stimulating a multi-epitopic immune response to a tumor-associated antigen comprising administering to a host a complex formed from a soluble tumor-associated antigen and an IgG antibody or antigen binding fragment thereof that binds to a first epitope of the tumor-associated antigen, wherein said tumor-associated antigen is CA 125, and wherein the administration of the complex induces host antibodies reactive with at least one other epitope of the tumor-associated antigen.
20. The method of claim 19 , wherein the antibody is produced by the hybridoma having ATCC deposit number PTA-1883.
21. A method of treating an oncological disease comprising stimulating a multi-epitopic immune response to a tumor-associated antigen comprising administering to a host a complex formed from a soluble tumor-associated antigen and an IgG antibody or antigen binding fragment thereof that binds to a first epitope of the tumor-associated antigen, wherein said tumor-associated antigen is CA 125, and wherein the administration of the complex induces cytotoxic T cells reactive with the tumor-associated antigen.
22. The method of claim 21 , wherein the antibody is produced by the hybridoma having ATCC deposit number PTA-1883.
23. The method of any of claims 1 , 10 , 12 , 15 , 18 , 19 , and 21 , wherein the antibody is a non-human antibody.
24. The method of any of claims 1 , 10 , 12 , 15 , 18 , 19 , and 21 , wherein said antibody or antigen binding fragment thereof comprises an Fc portion that binds an Fcγ RII receptor.
25. The method of any of claims 1 , 10 , 12 , 15 , 18 , 19 , and 21 , wherein said antibody is an IgG1 antibody or an antigen-binding fragment thereof.
26. A method of treating an oncological disease comprising stimulating a multi-epitopic immune response to a tumor-associated antigen comprising: administering to a host a complex formed from a soluble tumor-associated antigen and an antibody or antigen binding fragment thereof that binds to a first epitope of the tumor-associated antigen,
wherein the tumor-associated antigen is CA 125, and the first epitope of the tumor-associated antigen is the epitope bound by an antibody produced by the hybridoma having ATCC deposit number PTA-1883, and,
wherein the administration of the complex induces host antibodies reactive with at least one other epitope of the tumor-associated antigen.
27. A composition suitable for administration to a host for altering immunogenicity of a tumor-associated antigen comprising a complex of a soluble tumor-associated antigen and an antibody or antigen binding fragment thereof that specifically binds to an epitope of the antigen, wherein said tumor-associated antigen is CA 125, and wherein administration of the composition to a host results in a multi-epitopic immune response including production of antibodies reactive with at least one other epitope of the tumor-associated antigen.
28. The composition of claim 27 , wherein the antibody is selected from the group consisting a monoclonal antibody, a single chain antibody, a humanized antibody, and a chimeric antibody.
29. The composition of claim 27 , wherein the antibody is a monoclonal antibody.
30. The composition of claim 27 , wherein the host is a human.
31. A composition suitable for administration to a host for altering immunogenicity of a tumor-associated antigen comprising a complex of a soluble tumor-associated antigen and an IgG antibody or antigen binding fragment thereof that specifically binds to an epitope of the antigen, wherein said tumor-associated antigen is CA 125, and wherein administration of the composition to a host results in a multi-epitopic immune response including production of antibodies reactive with at least one other epitope of the tumor-associated antigen.
32. The composition of claim 27 or 31 , wherein the antibody is a non-human antibody.
33. The composition of claim 27 or 31 , wherein said antibody or antigen binding fragment thereof comprises an Fc portion that binds an Fcγ RII receptor.
34. The composition of claim 27 or 31 , wherein said antibody is an IgG1 antibody or an antigen-binding fragment thereof.
35. The composition of claim 27 , or 31 , wherein the antigen is a human antigen.
36. The composition of claim 31 , wherein the antibody is produced by the hybridoma having ATCC deposit number PTA-1883.
37. A composition suitable for administration to a host for altering immunogenicity of a tumor-associated antigen comprising a complex of CA 125 and a monoclonal antibody produced by the hybridoma having ATCC deposit number PTA-1883 or antigen binding fragment thereof that specifically binds to an epitope of CA 125, wherein administration of the composition to a host results in a multi-epitopic immune response including production of antibodies reactive with at least one other epitope of CA 125.