Antitumor activity of anti-C-ERC/mesothelin monoclonal antibody in vivo

Cancer Science
Koichi InamiOkio Hino

Abstract

Mesothelioma is an aggressive cancer often caused by chronic asbestos exposure, and its prognosis is very poor despite the therapies currently used. Due to the long latency period between asbestos exposure and tumor development, the worldwide incidence will increase substantially in the next decades. Thus, novel effective therapies are warranted to improve the prognosis. The ERC/mesothelin gene (MSLN) is expressed in wide variety of human cancers, including mesotheliomas, and encodes a precursor protein cleaved by proteases to generate C-ERC/mesothelin and N-ERC/mesothelin. In this study, we investigated the antitumor activity of C-ERC/mesothelin-specific mouse monoclonal antibody, 22A31, against tumors derived from a human mesothelioma cell line, ACC-MESO-4, in a xenograft experimental model using female BALB/c athymic nude mice. Treatment with 22A31 did not inhibit cell proliferation of ACC-MESO-4 in vitro; however, therapeutic treatment with 22A31 drastically inhibited tumor growth in vivo. 22A31 induced antibody-dependent cell-mediated cytotoxicity by natural killer (NK) cells, but not macrophages, in vitro. Consistently, the F(ab')(2) fragment of 22A31 did not inhibit tumor growth in vivo, nor did it induce antibody-depend...Continue Reading

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Citations

Mar 21, 2013·Journal of Gastroenterology·Futoshi KawamataSatoru Todo
May 17, 2014·Expert Review of Anticancer Therapy·Sabina Antonela AntoniuDidona Ungureanu
Aug 28, 2015·Cancer Science·Misa Imai, Oino Hino
Oct 16, 2012·International Journal of Oncology·Futoshi KawamataSatoru Todo
May 22, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shinji AbeYasuhiko Nishioka

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