論文 - 詳細
| RRC ID | 57974 |
|---|---|
| 著者 | Kanagawa N, Yanagawa T, Nakagawa T, Okada N, Nakagawa S. |
| タイトル | Tumor vessel-injuring ability improves antitumor effect of cytotoxic T lymphocytes in adoptive immunotherapy. |
| ジャーナル | Cancer Gene Ther |
| Abstract |
Angiogenesis is required for normal physiologic processes, but it is also involved in tumor growth, progression and metastasis. Here, we report the development of an immune-based antiangiogenic strategy based on the generation of T lymphocytes that possess killing specificity for cells expressing vascular endothelial growth factor receptor 2 (VEGFR2). To target VEGFR2-expressing cells, we engineered cytotoxic T lymphocyte (CTL) expressing chimeric T-cell receptors (cTCR-CTL) comprised of a single-chain variable fragment (scFv) against VEGFR2 linked to an intracellular signaling sequence derived from the CD3ζ chain of the TCR and CD28 by retroviral gene transduction methods. The cTCR-CTL exhibited efficient killing specificity against VEGFR2 and a tumor-targeting function in vitro and in vivo. Reflecting such abilities, we confirmed that the cTCR-CTL strongly inhibited the growth of a variety of syngeneic tumors after adoptive transfer into tumor-bearing mice without consequent damage to normal tissue. In addition, CTL expressing both cTCR and tumor-specific TCR induced complete tumor regression due to enhanced tumor infiltration by the CTL and long-term antigen-specific function. These findings provide evidence that the tumor vessel-injuring ability improved the antitumor effect of CTLs in adoptive immunotherapy for a broad range of cancers by inducing immune-mediated destruction of the tumor neovasculature. |
| 巻・号 | 20(1) |
| ページ | 57-64 |
| 公開日 | 2013-1-1 |
| DOI | 10.1038/cgt.2012.85 |
| PII | cgt201285 |
| PMID | 23175243 |
| PMC | PMC3534155 |
| MeSH | Adoptive Transfer Animals Carcinoma, Lewis Lung / blood supply Carcinoma, Lewis Lung / immunology Carcinoma, Lewis Lung / therapy* Cell Line, Tumor Female Humans Immunotherapy, Adoptive* Kidney / pathology Mice Mice, Inbred BALB C Mice, Inbred C57BL Neoplasm Transplantation Neovascularization, Pathologic / immunology Neovascularization, Pathologic / therapy Receptors, Antigen, T-Cell / biosynthesis Recombinant Fusion Proteins / biosynthesis Single-Chain Antibodies / biosynthesis T-Lymphocytes, Cytotoxic / immunology* T-Lymphocytes, Cytotoxic / metabolism T-Lymphocytes, Cytotoxic / transplantation Vascular Endothelial Growth Factor Receptor-2 / immunology Vascular Endothelial Growth Factor Receptor-2 / metabolism Wound Healing / immunology |
| 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 | 14 |
| 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 | LLC(RCB0558) |