論文 - 詳細
| RRC ID | 56125 |
|---|---|
| 著者 | Li HK, Hasegawa S, Nakajima NI, Morokoshi Y, Minegishi K, Nagatsu K. |
| タイトル | Targeted cancer cell ablation in mice by an α-particle-emitting astatine-211-labeled antibody against major histocompatibility complex class I chain-related protein A and B. |
| ジャーナル | Biochem Biophys Res Commun |
| Abstract |
Major histocompatibility complex class I chain-related protein A and B (MICA/B) are ligands of the immune receptor, natural-killer group 2 member D. MICA/B expression is often found in several types of cancer but is restricted in normal tissues. Here, we show that an α-particle emitting astatine-211 (211At)-labeled antibody targeting MICA/B (211At-anti MICA/B Ab) efficiently ablates cancer cells in vitro and in vivo. We generated 211At-anti MICA/B Ab, an anti-MICA/B antibody conjugated with a highly cytotoxic α-particle emitting radionuclide 211At. 211At-anti MICA/B Ab binds to human osteosarcoma SaOS2 and U2OS cells that exhibit high levels of MICA/B expression and efficiently kills those cells in vitro. Biodistribution analysis using xenograft mouse models of HCT116 p53-/- positive for MICA/B expression, showed increased 211At in the xenografts for up to 22 h after injection as time proceeded. A single dose of 211At-anti MICA/B Ab (1 MBq) showed significant reduction in the tumor growth rate of HCT116 p53-/- xenografts compared to 211At-labeled mouse IgG (1 MBq) at 21 days after injection. No body weight loss and erythrocytopenia was evident in mice that received 211At-anti MICA/B. Leukocytopenia and thrombocytopenia were observed within a week after 211At-anti MICA/B injection, but counts of red blood cells and platelets were recovered to control levels at about 3-4 weeks after injection. Taken together, these data strongly demonstrate that targeted α-particle therapy using 211At-anti-MICA/B Ab emitting highly cytotoxic α-particles is a potential new therapeutic option for several types of cancer. |
| 巻・号 | 506(4) |
| ページ | 1078-1084 |
| 公開日 | 2018-12-2 |
| DOI | 10.1016/j.bbrc.2018.10.157 |
| PII | S0006-291X(18)32342-8 |
| PMID | 30409432 |
| MeSH | Alpha Particles / therapeutic use* Animals Antibodies / immunology* Astatine / pharmacology* Cell Line, Tumor Cytotoxicity, Immunologic / drug effects Female Histocompatibility Antigens Class I / immunology* Humans Mice, Inbred BALB C Mice, Nude Neoplasms / therapy* Tissue Distribution / drug effects |
| IF | 2.705 |
| 引用数 | 1 |
| 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 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 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 | Saos-2(RCB0428) HCT116(RCB2979) HFL-III(RCB0523) HeLa |