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Antitumor activity of anti-C-ERC/mesothelin monoclonal antibody in vivo
Koichi Inami,
Masaaki Abe, Kazuyoshi Takeda,
Yoshiaki Hagiwara,
Masahiro Maeda,
Tatsuya Segawa,
Masafumi Suyama, Sumio Watanabe, Okio Hino,
Koichi Inami
Departments of Pathology and Oncology
Gastroenterology
Search for more papers by this authorKazuyoshi Takeda
Immunology, Juntendo University School of Medicine, Tokyo
Search for more papers by this authorYoshiaki Hagiwara
Departments of Pathology and Oncology
Immuno-Biological Laboratories Co., Ltd, Gunma, Japan
Search for more papers by this authorMasahiro Maeda
Immuno-Biological Laboratories Co., Ltd, Gunma, Japan
Search for more papers by this authorTatsuya Segawa
Immuno-Biological Laboratories Co., Ltd, Gunma, Japan
Search for more papers by this authorCorresponding Author
Okio Hino
Departments of Pathology and Oncology
To whom correspondence should be addressed.E-mail: [email protected]Search for more papers by this authorKoichi Inami,
Masaaki Abe, Kazuyoshi Takeda,
Yoshiaki Hagiwara,
Masahiro Maeda,
Tatsuya Segawa,
Masafumi Suyama, Sumio Watanabe, Okio Hino,
Koichi Inami
Departments of Pathology and Oncology
Gastroenterology
Search for more papers by this authorKazuyoshi Takeda
Immunology, Juntendo University School of Medicine, Tokyo
Search for more papers by this authorYoshiaki Hagiwara
Departments of Pathology and Oncology
Immuno-Biological Laboratories Co., Ltd, Gunma, Japan
Search for more papers by this authorMasahiro Maeda
Immuno-Biological Laboratories Co., Ltd, Gunma, Japan
Search for more papers by this authorTatsuya Segawa
Immuno-Biological Laboratories Co., Ltd, Gunma, Japan
Search for more papers by this authorCorresponding Author
Okio Hino
Departments of Pathology and Oncology
To whom correspondence should be addressed.E-mail: [email protected]Search for more papers by this authorAbstract
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-dependent cell mediated cytotoxicity (ADCC) in vitro. Moreover, NK cell depletion diminished the antitumor effect of 22A31. Thus, 22A31 induced NK cell-mediated ADCC and exerted antitumor activity in vivo. 22A31 could have potential as a therapeutic tool to treat C-ERC/mesothelin-expressing cancers including mesothelioma.
(Cancer Sci 2010; 101: 969–974)
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