Surrogate therapeutic endpoint for anti-CTLA4-based immunotherapy of disease
View Patent ↗The present invention provides a method of treatment using human sequence antibodies against human CTLA-4. In particular, methods of treating cancer are provided.
1. A method for treating cancer in a patient in need of such treatment, which method comprises administering an anti-CTLA-4 antibody in a dosage sufficient to induce a breakthrough event and detecting the breakthrough event.
2. The method of claim 1 wherein the breakthrough event is an autoimmune response.
3. The method of claim 1 wherein the breakthrough event is a severe, life-threatening, or disabling adverse event.
4. The method of claim 1 , wherein the breakthrough event is induced by administering escalating doses of anti-CTLA-4 antibody.
5. The method of claim 1 , wherein the breakthrough event is induced by administering anti-CTLA-4 at decreasing dosage intervals.
6. The method of claim 1 , wherein the breakthrough event comprises a manifestation of non-tumor related autoimmunity.
7. The method of claim 1 wherein the cancer is an immunologically sensitive tumor.
8. The method of claim 1 wherein the cancer is malignant melanoma.
9. A method for treating melanoma in a patient in need of such treatment, which method comprises administering anti-CTLA-4 antibody 10D1 in a dosage sufficient to induce a breakthrough event and detecting the breakthrough event.
10. The method of claim 9 wherein the breakthrough event is an autoimmune response.
11. The method of claim 9 wherein the breakthrough event is a severe, life-threatening, or disabling adverse event.
12. The method of claim 11 , wherein the breakthrough event is selected from the group consisting of diarrhea, enterocolitis, dermatitis, hypophysitis, panhypopituitarism, rash, and pruritis.
13. The method of claim 9 , wherein the breakthrough event is induced by administering escalating doses of anti-CTLA-4 antibody.
14. The method of claim 9 , wherein the breakthrough event is induced by administering anti-CTLA-4 at decreasing dosage intervals.
15. The method of claim 9 , wherein the breakthrough event is selected from the group consisting of dermatitis, vitiligo, and enterocolitis.
16. The method of claim 1 , where an additional therapeutic agent for treating the cancer is administered.
17. The method of claim 1 , where an additional therapeutic agent for treating the breakthrough event is administered.
18. The method of claim 3 , wherein the breakthrough event is selected from the group consisting of diarrhea, enterocolitis, dermatitis, hypophysitis, panhypopituitarism, rash, and pruritis.
19. The method of claim 1 , wherein the breakthrough event is selected from the group consisting of dermatitis, vitiligo, and enterocolitis.