Surrogate therapeutic endpoint for anti-CTLA-4 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 determining a therapeutically effective dosage regimen of anti-CTLA -4 antibody for the treatment of cancer, which method comprises adjusting a dose or dosage schedule, or both, of an anti-CTLA-4 antibody in a subject until observing a breakthrough event in the subject, which dose is the therapeutically effective dosage regimen.
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 is a peripheral 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. The method of claim 1 , wherein the breakthrough event is selected from the group consisting of dermatitis, vitiligo, and enterocolitis.
10. The method of claim 3 , wherein the breakthrough event is selected from the group consisting of diarrhea, enterocolitis, dermatitis, hypophysitis, panhypopituitarism, rash, and pruritis.