論文 - 詳細
| RRC ID | 18193 |
|---|---|
| 著者 | Takenouchi M, Hirai S, Sakuragi N, Yagita H, Hamada H, Kato K. |
| タイトル | Epigenetic modulation enhances the therapeutic effect of anti-IL-13R(alpha)2 antibody in human mesothelioma xenografts. |
| ジャーナル | Clin Cancer Res |
| Abstract |
PURPOSE:The interleukin-13 receptor α2 (IL-13Rα2) is expressed by a variety of human malignant cells. Here, we have examined the constitutive surface expression and the epigenetic regulation of IL-13Rα2 by human mesothelioma. We have also investigated the therapeutic effect of the DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-aza-dC) and anti-IL-13Rα2 monoclonal antibody on mesothelioma xenografts. EXPERIMENTAL DESIGN:Cell surface expression of IL-13Rα2 by various lung carcinomas was analyzed using flow cytometry. Therapeutic effects of anti-IL-13Rα2 and 5-aza-dC were investigated using antibody-dependent cellular cytotoxicity and proliferation assays and by monitoring the survival of mesothelioma-bearing mice. RESULTS:We found that human malignant mesotheliomas expressed surface IL-13Rα2 on their surface and that it was upregulated by treatment with 5-aza-dC. This augmented expression of IL-13Rα2 resulted in growth inhibition of the mesothelioma cells when cocultured with anti-IL-13Rα2 and effector cells, such as splenocytes and peritoneal exudate cells. The growth inhibition of mesothelioma cells was mediated by IFN-γ that was only detected in the supernatant when effector cells were exposed to 5-aza-dC-treated tumors in the presence of anti-IL-13Rα2. Compared with the control or either regimen alone, in vivo administration of anti-IL-13Rα2 in combination with 5-aza-dC significantly prolonged the survival of mice with mesothelioma xenografts. CONCLUSIONS:These observations indicate a promising role for IL-13Rα2 as a target for antibody treatment in malignant mesothelioma, and, in combination with epigenetic regulation by a DNA methylation inhibitor, suggest the potential for a novel strategy to enhance therapeutic potency. |
| 巻・号 | 17(9) |
| ページ | 2819-29 |
| 公開日 | 2011-5-1 |
| DOI | 10.1158/1078-0432.CCR-10-2986 |
| PII | 1078-0432.CCR-10-2986 |
| PMID | 21357681 |
| MeSH | Animals Antibodies, Monoclonal / administration & dosage* Antibodies, Monoclonal / therapeutic use Antimetabolites, Antineoplastic / administration & dosage Antimetabolites, Antineoplastic / pharmacology Azacitidine / administration & dosage Azacitidine / analogs & derivatives* Azacitidine / pharmacology Cell Line, Tumor Combined Modality Therapy Decitabine Drug Synergism Epigenesis, Genetic / drug effects* Epigenesis, Genetic / physiology Female HCT116 Cells Humans Immunotherapy Interleukin-13 Receptor alpha2 Subunit / antagonists & inhibitors Interleukin-13 Receptor alpha2 Subunit / immunology* Mesothelioma / drug therapy Mesothelioma / genetics Mesothelioma / pathology Mesothelioma / therapy* Mice Mice, Inbred BALB C Mice, Inbred ICR Mice, Knockout Mice, Nude Xenograft Model Antitumor Assays |
| IF | 10.107 |
| 引用数 | 17 |
| WOS 分野 | ONCOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | MKN45(RCB1001) |