論文 - 詳細
| RRC ID | 57865 |
|---|---|
| 著者 | Nishimura T, Mitsunaga M, Ito K, Kobayashi H, Saruta M. |
| タイトル | Cancer neovasculature-targeted near-infrared photoimmunotherapy (NIR-PIT) for gastric cancer: different mechanisms of phototoxicity compared to cell membrane-targeted NIR-PIT. |
| ジャーナル | Gastric Cancer |
| Abstract |
BACKGROUND:Near-infrared photoimmunotherapy (NIR-PIT) constitutes a new class of molecular-targeted theranostics utilizing monoclonal antibody (mAb)-photosensitizer conjugates and NIR light. In this study, we developed a new type of NIR-PIT targeting vascular endothelial growth factor receptor 2 (VEGFR-2) expressed on vascular endothelium in an experimental gastric cancer model and evaluated the feasibility by comparing conventional NIR-PIT targeting cancer cell membrane in vitro and in vivo. METHODS:HER2-positive human gastric cancer cells, NCI-N87, were used for the experiments. Anti-HER2 mAb, trastuzumab and anti-VEGFR-2 mAb, DC101 were conjugated to photosensitizer, IR700. Phototoxicity in response to NIR-PIT were investigated in vitro and in vivo. Microvessel densities, as an indicator of angiogenesis, were counted in harvested xenografts after NIR-PIT to elucidate the mechanism. RESULTS:DC101-IR700 did not induce phototoxic effect in vitro because of the absence of expression of VEGFR-2 in NCI-N87 cancer cells. However, it induced an antitumor effect in NCI-N87 xenograft tumors accompanied with damage in tumor neovasculature as determined by decreasing tumor microvessel density, which represents a different mechanism than that of conventional NIR-PIT targeting antigens expressed on the tumor cell membrane. CONCLUSION:We demonstrated a new approach of NIR-PIT utilizing a target on vascular endothelium, such as VEGFR-2, and this treatment might lead to the development of a new therapeutic strategy for human gastric cancer. |
| 巻・号 | 23(1) |
| ページ | 82-94 |
| 公開日 | 2020-1-1 |
| DOI | 10.1007/s10120-019-00988-y |
| PII | 10.1007/s10120-019-00988-y |
| PMID | 31302791 |
| PMC | PMC8189161 |
| MeSH | Animals Antibodies, Monoclonal / pharmacokinetics Antibodies, Monoclonal / pharmacology Cell Death / drug effects Cell Line, Tumor Cell Membrane / drug effects Female Humans Immunotherapy / methods* Mice, Inbred BALB C Microvessels / drug effects Microvessels / pathology Molecular Targeted Therapy Photosensitizing Agents / pharmacokinetics Photosensitizing Agents / pharmacology Phototherapy / methods* Receptor, ErbB-2 / metabolism Stomach Neoplasms / blood supply Stomach Neoplasms / pathology Stomach Neoplasms / therapy* Tissue Distribution Trastuzumab / pharmacokinetics Trastuzumab / pharmacology Vascular Endothelial Growth Factor Receptor-2 / metabolism Xenograft Model Antitumor Assays |
| IF | 7.088 |
| 引用数 | 2 |
| リソース情報 | |
| ヒト・動物細胞 | MKN45(RCB1001) |