| RRC ID |
56033
|
| 著者 |
Yu M, Luo H, Fan M, Wu X, Shi B, Di S, Liu Y, Pan Z, Jiang H, Li Z.
|
| タイトル |
Development of GPC3-Specific Chimeric Antigen Receptor-Engineered Natural Killer Cells for the Treatment of Hepatocellular Carcinoma.
|
| ジャーナル |
Mol Ther
|
| Abstract |
Chimeric antigen receptor (CAR)-modified natural killer (NK) cells represent a promising immunotherapeutic modality for cancer treatment. However, their potential utilities have not been explored in hepatocellular carcinoma (HCC). Glypian-3 (GPC3) is a rational immunotherapeutic target for HCC. In this study, we developed GPC3-specific NK cells and explored their potential in the treatment of HCC. The NK-92/9.28.z cell line was established by engineering NK-92, a highly cytotoxic NK cell line with second-generation GPC3-specific CAR. Exposure of GPC3+ HCC cells to this engineered cell line resulted in significant in vitro cytotoxicity and cytokine production. In addition, soluble GPC3 and TGF-β did not significantly inhibit the cytotoxicity of NK-92/9.28.z cells in vitro, and no significant difference in anti-tumor activities was observed in hypoxic (1%) conditions. Potent anti-tumor activities of NK-92/9.28.z cells were observed in multiple HCC xenografts with both high and low GPC3 expression, but not in those without GPC3 expression. Obvious infiltration of NK-92/9.28.z cells, decreased tumor proliferation, and increased tumor apoptosis were observed in the GPC3+ HCC xenografts. Similarly, efficient retargeting on primary NK cells was achieved. These results justified clinical translation of this GPC3-specific, NK cell-based therapeutic as a novel treatment option for patients with GPC3+ HCC.
|
| 巻・号 |
26(2)
|
| ページ |
366-378
|
| 公開日 |
2018-2-7
|
| DOI |
10.1016/j.ymthe.2017.12.012
|
| PII |
S1525-0016(17)30609-3
|
| PMID |
29339014
|
| PMC |
PMC5835122
|
| MeSH |
Animals
Carcinoma, Hepatocellular / immunology*
Carcinoma, Hepatocellular / therapy*
Cell Line, Tumor
Cytokines / metabolism
Epitopes
Gene Expression
Gene Order
Genetic Vectors / genetics
Glypicans / genetics
Glypicans / immunology*
Heterografts
Humans
Immunophenotyping
Immunotherapy, Adoptive
Killer Cells, Natural / immunology*
Killer Cells, Natural / metabolism*
Lentivirus / genetics
Liver Neoplasms / immunology*
Liver Neoplasms / therapy*
Mice
Phenotype
Receptors, Chimeric Antigen / genetics
Receptors, Chimeric Antigen / metabolism*
Transduction, Genetic
|
| IF |
8.402
|
| 引用数 |
24
|
| リソース情報 |
| ヒト・動物細胞 |
HuH-7 |
