Abstract 4584: Pre-clinical studies of a novel antibody to treat pancreatic and colorectal cancers

Abstract

Abstract Introduction: NPC-1C is a chimeric monoclonal antibody being developed as a novel biological treatment for pancreatic and colorectal cancers. NPC-1C appears to recognize a variant form of MUC5AC expressed specifically by human pancreatic and colorectal tumor tissues and cell lines. Here we show pre-clinical studies in preparation for testing this therapeutic for a Phase I clinical trial. Methods: The NPC-1C antibody was selected from a panel of hybridomas generated from mice immunized with semi-purified membrane-associated proteins derived from biologically screened, pooled human allogeneic colon cancer tissues. In vitro assays and in vivo studies were performed to characterize the GMP-grade antibody. Results: Here we show that NPC-1C reacts with colorectal and pancreatic tumor tissues, but does not cross-react with normal human tissues, except for occasional, weak binding to certain GI tract tissues, which may indicate a pre-malignant state. The NPC-1C antibody exhibits cell-specific binding and ADCC activity against human colorectal and pancreatic tumor cells, but not against control tumor cell lines. In vivo, the anti-tumor efficacy of NPC-1C was tested using pre-established subcutaneous human tumor xenograft models. The data showed significant, and reproducible, anti-tumor action, including some complete tumor regressions. The pre-clinical toxicity profile of NPC-1C in normal BALB/c mice demonstrated little, if any, toxicity following single or multiple intravenous injections. The bio-distribution of radiolabeled NPC-1C in mice with pre-established human tumors revealed specific accumulation of NPC-1C at the tumor site, with little or no binding or accumulation in several major organ systems. Finally, the cytokine and antibody responses to NPC-1C were studied in the pre-clinical mouse model. Although anti-NPC-1C antibodies were detected (as expected) in a time-dependent fashion, there were no changes detect in Type I and Type II cytokines either 3 days or 14 days after intravenous administration. Conclusions: The pre-clinical development of NPC-1C indicates that it is safe and efficacious, and suggests that it may have clinical activity in patients whose tumor expresses the variant MUC5AC epitope. The potential clinical application for this antibody was bolstered by showing approximately 50-70% of human pancreatic and colon tumor tissues stained positively with NPC-1C. The therapeutic antibody is now being tested in a Phase I clinical trial in patients with advanced pancreatic and colorectal cancer. 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 4584. doi:10.1158/1538-7445.AM2011-4584