Abstract LB-262: Phosphatidylserine-targeting antibody synergizes with anti-PD-1 antibody to inhibit tumor growth in K1735 mouse melanoma model

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA A large body of evidence indicates that PS is a major player in tumor-associated immunosuppression, including the induction and expansion of immune suppressor cells, such as MDSCs and M2 macrophages, and the production of immunosuppressive cytokines, such as TGF-beta and IL-10. Furthermore, PS also inhibits DCs maturation and antigen presentation. Thus, PS is a critical target for cancer immunotherapy. We have previously shown that anti-PS antibody can override PS-driven immunosuppression and re-program the tumor microenvironment from immunosuppressive to immunosupportive, breaks tumor immune tolerance and elicits potent de novo antitumor T-cell immunity. In the present study, we examined the combination of anti-PD-1 with anti-PS antibody in K1735 mouse melanoma model. Tumor-bearing mice were treated with each antibody alone or the combination at 2.5 mg/kg, twice a week. The combination treatment showed significantly superior tumor growth inhibition than with either antibody alone, animals treated with the combination survived significantly longer than with either antibody alone. Flow cytometry analysis showed the combination has the highest ratio of tumor-infiltrating immune effector to suppressor cells. Finally, no toxicity was observed in all treatment groups following multiple treatment doses. These data suggest that combination of PS blockade with immune checkpoint blockade represents a promising combinatorial strategy for cancer immunotherapy. Citation Format: Xianming Huang, dan Ye, Rolf Brekken, Yi Yin. Phosphatidylserine-targeting antibody synergizes with anti-PD-1 antibody to inhibit tumor growth in K1735 mouse melanoma model. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-262. doi:10.1158/1538-7445.AM2014-LB-262