Abstract 2428: PPMX-2017: Antibody against CDH3 with potent efficacy against lung cancer

Abstract

Abstract Cadherin 3/P-cadherin (CDH3) is a member of cadherin family proteins involved in the cell-cell adhesion. Based on a genome-wide cDNA microarray analysis of pancreatic cancer, we found that CDH3 is overexpressed in pancreatic cancer. We also confirmed by our immunohistochemistry study that CDH3 protein was expressed highly in pancreatic, lung, colon and other types of cancer tissues but not in normal tissues. Since CDH3 is a transmembrane glycoprotein and overexpressed in cancer tissues, it is an attractive therapeutic target for various kinds of cancer. In this present study, we generated a series of monoclonal antibodies against CDH3 and evaluated their anti-tumor effect both in vitro and in vivo. PPMX2017, an antibody from the series, is an anti-human CDH3 specific mouse IgG2a antibody. The in vitro studies demonstrated that PPMX2017 elicited strong antibody dependent cellular cytotoxicity (ADCC) activity on CDH3-positive cancer cell lines (lung cancer: NCI-H358 and A431, pancreatic cancer: KLM1 and Bxpc3.). Furthermore, PPMX2017 showed a significant antitumor effect in a therapeutic xenograft model of lung cancer where NCI-H358 cell-generated tumors grew to 70∼90 mm3 before administration of this antibody. PPMX2017 suppressed tumor growth by 60∼80% compared with control IgG in a dose range of 0.3mg∼5mg/kg. These findings show that CDH3 is a potential target for cancer therapy and PPMX2017 is a candidate for the development of antibody therapeutics. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2428.