論文 - 詳細
| 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 |
| 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 | 19 |
| 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 | HuH-7 |