Abstract 4566: AGS-1C4D4: A fully human anti-PSCA antibody inhibits tumor formation and metastasis in orthotopic models of pancreatic cancer

Prostate stem cell antigen (PSCA) is a cysteine-rich cell surface glycoprotein expressed in about 50% of pancreatic and prostate cancers. AGS-PSCA is a hybridoma-derived fully human IgG1κ monoclonal antibody (MAb) targeting PSCA previously reported to have anti-tumor efficacy in prostate and pancreatic tumor models. AGS-1C4D4 is a CHO-derived antibody generated from the same gene as AGS-PSCA, with similar specificity and binding affinity to PSCA (Kd = 2.0 × 10-10M). Since hybridoma and CHO-derived MAbs displayed disparate glycosylation patterns by mass spectroscopy, we further evaluated their MAb effector functions. AGS-1C4D4 was found to have more potent ADCC activity in vitro on PSCA-expressing pancreatic cell lines, HPAC and Panc0203, using human PBMCs from multiple normal donors. However, both MAbs were similarly effective in mediating CDC on PSCA-expressing recombinant B300.19 cells. Deglycosylation greatly reduced the relative ADCC and CDC activities of both MAbs compared to their intact versions. Additional studies to elucidate the role of the effector functions of AGS-1C4D4 are currently being conducted in vivo using intact and deglycosylated MAbs and will be presented. While neither intact antibody had any direct cytotoxic activity on HPAC cells in vitro, both MAbs significantly inhibited tumor formation, local invasion and metastases to distant sites in orthotopic HPAC xenograft tumor models in vivo. In addition, AGS-1C4D4 significantly inhibited the growth and metastasis of established orthotopic HPAC tumors in combination with Gemcitabine. AGS-1C4D4 is currently being evaluated in a Phase 2 clinical study for pancreatic cancer in combination with Gemcitabine. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4566. doi:10.1158/1538-7445.AM2011-4566