Abstract B097: Development of a mouse-human chimeric antibody against human CXADR having a potent antitumor activity in animal models

Abstract

Abstract Coxsackievirus and adenovirus receptor (CXADR) is a single-pass transmembrane protein that is expressed on some cancers including prostate, lung, and brain tumor tissues. We previously developed a mouse monoclonal antibody against human CXADR, mu6G10A, and found that mu6G10A significantly exerts an anti-tumor activity against various human cancer cell lines expressing CXADR through antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) activities. In this study, we have developed a mouse-human chimeric anti-CXADR antibody, ch6G10A, from mu6G10A, and evaluated its anti-tumor activity. As a result, in vitro experiments clearly showed that ch6G10A possesses binding, ADCC, and CDC activities against human prostate cancer DU-145 cells expressing CXADR like mu6G10A. In vivo xenograft models showed that ch6G10A exerts a significant anti-tumor activity against DU-145 cells when human NK cells were co-injected. These results indicate that a mouse-human chimeric anti-CXADR antibody, ch6G10A, has a therapeutic potential as a novel anti-tumor antibody drug. Citation Format: Manabu Kawada, Shuichi Sakamoto, Hiroyuki Inoue, Mika Kaneko, Satoshi Ogasawara, Masunori Kajikawa, Sakiko Urano, Shun-ichi Ohba, Yukinari Kato. Development of a mouse-human chimeric antibody against human CXADR having a potent antitumor activity in animal models [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr B097. doi:10.1158/1535-7163.TARG-19-B097