Generation and evaluation of a chimeric antibody against coxsackievirus and adenovirus receptor for cancer therapy

摘要

Coxsackievirus and adenovirus receptor (CAR) is a single‐pass transmembrane protein that is associated with adenoviral infection. is involved in the formation of epithelial tight junctions and promotes tumor growth in some cancers. Previously, we developed mouse monoclonal antibodies against human and found that one, mu6G10A, significantly inhibited tumor growth in xenografts of human cancer cells. Herein, we generated and characterized a mouse‐human chimeric anti‐ antibody (ch6G10A) from mu6G10A. ch6G10A had binding activity, inducing antibody‐dependent cellular cytotoxicity and complement‐dependent cytotoxicity, and in vivo anti‐tumor activity against ‐expressing prostate cancer ‐145 cells. In addition, cancer tissue array analysis confirmed that is highly expressed in neuroendocrine lung cancers including small cell lung cancer, and treatment with ch6G10A effectively inhibited in vivo subcutaneous tumor growth of ‐H69 small cell lung cancer cells in nude mice. Moreover, treatment with mu6G10A effectively inhibited both in vivo orthotopic tumor growth and distant metastatic formation in mouse xenograft models of a highly metastatic subline of human small cell lung cancer 273 cells. These results suggest that targeting therapy to with a therapeutic antibody might be effective against several cancer types including small cell lung cancer.