Abstract 2517: Potent antitumor activity of AbGn-ADC, a humanized monoclonal antibody conjugated with dolastatin analogue, to gastric and pancreatic cancers expressing AbGn carbohydrate epitope

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL AbGn is a glycotope-specific humanized monoclonal antibody recognizing Lewisa- like carbohydrate expressed in gastric and pancreatic cancer cells. While AbGn binding to normal tissues is restricted to only luminal surface of the epithelium in gastro-intestinal track and secretory glands, about 50% of gastric and pancreatic cancer samples tested express AbGn epitope and can be recognized by AbGn antibody. FACS analysis and confocal microscopic studies demonstrated extensive internalization of AbGn after binding to the cell surface. The internalized AbGn co-localized with lysosomal marker LAMP1, suggesting that AbGn-mediated internalization followed the lysosomal pathway. A novel antibody-drug conjugate (AbGn-ADC) was generated by linking AbGn to a dolastatin analogue, a potent inhibitor of microtubulin polymerization, through a dipeptide-based cleavable linker. This AbGn-ADC was evaluated for antitumor activity in vitro and in mouse xenograft models. AbGn-ADC eliminated cancer cell lines with nanomolar potency in vitro. No cell death could be detected in SW480 cells, a gastric cell line with no AbGn epitope expression, suggesting high selectivity of AbGn-ADC. When used to treat mice with established human gastric (SNU-16) or pancreatic (Panc.02.03B) cancer xenografts, AbGn-ADC significantly reduced the size of the established tumors (p<0.01). No body weight loss or signs of toxicity was observed in AbGn-ADC treated mice. These findings support the potential of further development of AbGn-ADC for treating gastric and pancreatic cancers. Data from pre-clinical AbGn-ADC tolerability study in relevant non-human primate will be presented. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2517. doi:1538-7445.AM2012-2517