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

Shuichi Sakamoto, Hiroyuki Inoue, Mika K. Kaneko, Satoshi Ogasawara, Masunori Kajikawa, Sakiko Urano, Shun ichi Ohba, Yukinari Kato, Manabu Kawada

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Coxsackievirus and adenovirus receptor (CAR) is a single-pass transmembrane protein that is associated with adenoviral infection. CAR is involved in the formation of epithelial tight junctions and promotes tumor growth in some cancers. Previously, we developed mouse monoclonal antibodies against human CAR 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-CAR antibody (ch6G10A) from mu6G10A. ch6G10A had binding activity, inducing antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity, and in vivo anti-tumor activity against CAR-expressing prostate cancer DU-145 cells. In addition, cancer tissue array analysis confirmed that CAR is highly expressed in neuroendocrine lung cancers including small cell lung cancer, and treatment with ch6G10A effectively inhibited in vivo subcutaneous tumor growth of NCI-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 DMS273 cells. These results suggest that targeting therapy to CAR with a therapeutic antibody might be effective against several cancer types including small cell lung cancer.

Original languageEnglish
Pages (from-to)3595-3602
Number of pages8
JournalCancer science
Volume110
Issue number11
DOIs
Publication statusPublished - 2019 Nov 1

Keywords

  • CAR
  • mouse-human chimeric antibody
  • orthotopic transplantation model
  • prostate cancer
  • small cell lung cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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