論文 - 詳細
| RRC ID | 38232 |
|---|---|
| 著者 | Inami K, Abe M, Takeda K, Hagiwara Y, Maeda M, Segawa T, Suyama M, Watanabe S, Hino O. |
| タイトル | Antitumor activity of anti-C-ERC/mesothelin monoclonal antibody in vivo. |
| ジャーナル | Cancer Sci |
| 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-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. |
| 巻・号 | 101(4) |
| ページ | 969-74 |
| 公開日 | 2010-4-1 |
| DOI | 10.1111/j.1349-7006.2009.01463.x |
| PII | CAS1463 |
| PMID | 20100205 |
| MeSH | Animals Antibodies, Monoclonal / immunology Antibodies, Monoclonal / pharmacology Antibodies, Monoclonal / therapeutic use* Antibody-Dependent Cell Cytotoxicity / drug effects Antibody-Dependent Cell Cytotoxicity / immunology Female GPI-Linked Proteins Humans Killer Cells, Natural / immunology Killer Cells, Natural / metabolism Membrane Glycoproteins / immunology* Mesothelin Mesothelioma / therapy* Mice Mice, Inbred BALB C Mice, Nude Oncogene Proteins / immunology |
| IF | 4.966 |
| 引用数 | 13 |
| WOS 分野 | ONCOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 6 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | ACC-MESO-4(RCB2293) |