CTLA-4 based therapy (MDX-010)

CTLA-4 is a negative regulator of T cell activity. Antibodies to CTLA-4 have been shown to directly activate anti-tumor responses in a several syngeneic murine models. For less immunogenic murine tumors, anti-CTLA-4 treatment has anti-tumor activity when combined with vaccines or other therapeutic regimens. In order to explore the use of CTLA-4 blockade in human immunotherapy, we have developed and characterized an antibody to human CTLA-4 (MDX-010), derived from HuMAb mice, which blocks the binding of CTLA-4 to B7 ligands. MDX-010 was able to inhibit the growth of tumors in mice transgenic for human CTLA-4. Vaccination experiments and multiple dosing in primates were used to further define the activity and safety profiles of MDX-010. Several human clinical trials using MDX-010 have been completed and multiple trials are in progress; the clinical experience in these trials will be summarized.