Abstract 2850: Predicting anti-tumor responses to phosphatidylserine targeting antibodies using tumor imaging.

Abstract

Abstract Phosphatidylserine (PS) is a phospholipid normally residing in the inner leaflet of the plasma membrane and becomes exposed on tumor vascular endothelial cells and tumor cells in response to chemotherapy, irradiation and oxidative stresses in the tumor microenvironment. Binding of antibodies targeting PS on the tumor endothelial cells and tumors induces the recruitment of immune cells and engages the immune system to destroy tumor vasculature. The antibodies also enhance anti-tumor immunity by blocking the immunosuppressive action of PS. A chimeric PS-targeting antibody, bavituximab, is being used in combination with chemotherapy to treat patients with solid tumors in Phase II trials. Fully human antibody PGN635 binds PS through the interaction of beta-2-glycoprotein 1 (β2GP1) in the same manner as bavituximab. Using human PC-3 prostate tumor xenografts in SCID mice, we demonstrate that targeting of PS in tumors by PGN635 is enhanced by chemotherapy. Combination of PGN635 with docetaxel inhibited tumor growth compared to the control IgG plus docetaxel group (p<0.05). Near-infrared optical imaging of PS in tumors with PGN650, an F(ab’)2 antibody fragment of PGN635, showed tumor growth inhibition in mice treated with docetaxel correlates with PS expression levels in the tumors. Maximal uptake of the PS imaging was observed when chemotherapy was given 24 hours before the imaging probe. Citation Format: Jian Gong, Richard Archer, Van Nguyen, Christopher C.W. Hughes, Jeff Hutchins, Bruce Freimark. Predicting anti-tumor responses to phosphatidylserine targeting antibodies using tumor imaging. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2850. doi:10.1158/1538-7445.AM2013-2850