| 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
|
| リソース情報 |
| ヒト・動物細胞 |
Saos-2(RCB0428)
HCT116(RCB2979)
HFL-III(RCB0523)
HeLa |
