Abstract 2855: Anti-PSMA x anti-CD3 SCORPIONTM molecule inhibits tumor growth in vivo in mouse models of prostate cancer.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Background: Treatment of metastatic, castrate-resistant prostate cancer (CRPC) remains a highly unmet medical need. We have developed a bispecific SCORPIONTM (multi-specific protein therapeutic) molecule that redirects T cell cytotoxicity against cells expressing PSMA (Prostate Specific Membrane Antigen), a common prostate-cancer related antigen. The SCORPION molecule described here contains two pairs of binding domains, each targeting a unique antigen, linked to opposite ends of an immunoglobulin Fc domain to extend the half-life of the molecule in vivo. In these studies, we examine the ability of a SCORPION molecule targeting both CD3 and PSMA, to inhibit the growth of PSMA expressing tumors in vivo. Materials and Methods: NOD/SCID mice were implanted with the PSMA(+) prostate tumor cell line C4-2B and purified human T cells in one of two models. In a first model of residual disease, C4-2B cells were coimplanted subcutaneously with human T cells, and treatment with drug was initiated immediately. This model was run twice with T cells from two different human donors. In a second model of established disease, C4-2B cells were implanted subcutaneously and allowed to develop for 20 days, after which human T cells were injected intra-peritoneally, with subsequent administration of drug. Tumor growth was assessed by tumor volume and serum PSA, and tumor volume and weight loss were used as endpoints. Results: SCORPION molecules targeting PSMA and CD3 inhibited growth of PSMA(+) tumors in both model settings and significantly improved overall survival. Reduction in circulating serum PSA was also observed. Repeat studies using a second human T cell donor showed similar inhibition of tumor growth and overall survival. Inhibition of tumor growth was seen at doses in the low pmol range per mouse. Conclusions: These studies show that anti-PSMA x anti-CD3 SCORPION therapeutics redirect T cell cytotoxicity in in vivo xenograft models and merit further investigation as potential therapeutics in CRPC. Citation Format: Robert Miller, Hang Fang, Jessica Luke, Megan Aguilar, Ruth Chenault, John Kumer, Jennifer Wiens, Paul Algate, David Bienvenue, Catherine McMahan, Holly Nguyen, Robert Vessella, John Blankenship. Anti-PSMA x anti-CD3 SCORPIONTM molecule inhibits tumor growth in vivo in mouse models of prostate cancer. [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 2855. doi:10.1158/1538-7445.AM2013-2855