Abstract 2667: RG7287, a novel humanized anti-CDCP1 antibody with superior preclinical in vivo efficacy in combination with Paclitaxel

Abstract

Abstract CUB domain-containing protein 1 (CDCP1) is a transmembrane glycoprotein and a substrate of Src family kinase (SFK). It has been shown to be upregulated and significantly contributing to a number of different cancers, including colon, lung, breast, kidney, and pancreas cancer. High expression of CDCP1 has been shown to correlate with poor prognosis. CDCP1 is involved in the regulation of anoikis resistance, cell migration and invasion. We have recently described RG7287, a humanized glycoengineered therapeutic anti-CDCP1 antibody with a dual mode of action. (1) downregulation of the receptor from the cell surface, and (2) engaging immune effector functions such as antibody-dependent cellular cytotoxicity (ADCC). Upon ligation of RG7287 to CDCP1 an initial phosphorylation of CDCP1 occurs, this transient activation results in the down-regulation of CDCP1. RG7287 prohibits the transformation potential of CDCP1 and Src in focus formation assays. In vivo, RG7287 increased the survival time of mice bearing tumors of MCF7 cells stably expressing CDCP1 compared to untreated CDCP1 overexpressing MCF7 tumors. Treatment of three different xenograft models with RG7287 inhibited tumor growth. In this study we looked at the possibility of eradicating the tumors by combining RG7287 with paclitaxel. Combining the cytostatic with RG7287 increases tumor growth inhibition compared to RG7287 alone in one xenograft model. In another model the combination of RG7287 with paclitaxel leads to tumor stasis. These results indicate a potential combination therapy for RG7287. We also tested whether RG7287 inhibits metastasis in vivo. Using a metastasis model we could show convincing inhibition of metastasis. Citation Format: Gwendlyn Kollmorgen, Alexander Lifke, Adam Nopora, Frieder Bauss, Gerhard Niederfellner, Birgit Bossenmaier. RG7287, a novel humanized anti-CDCP1 antibody with superior preclinical in vivo efficacy in combination with Paclitaxel. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2667. doi:10.1158/1538-7445.AM2014-2667