論文 - 詳細
| RRC ID | 45209 |
|---|---|
| 著者 | Morisaki T, Hirano T, Koya N, Kiyota A, Tanaka H, Umebayashi M, Onishi H, Katano M. |
| タイトル | NKG2D-directed cytokine-activated killer lymphocyte therapy combined with gemcitabine for patients with chemoresistant metastatic solid tumors. |
| ジャーナル | Anticancer Res |
| Abstract |
Natural-killer group 2, member D (NKG2D) is an activating receptor found on activated natural killer cells and on activated T-cells, here termed cytokine-activated killer (CAK) cells. NKG2D ligands are expressed on various human cancer types. Gemcitabine is an anticancer drug which is a less immune-destructive agent than others. Herein, we investigated the clinical efficacy and the underlying mechanisms of a combination of CAK cell infusion therapy and gemcitabine. Twenty-three patients with disseminated carcinomas were treated with chemo-immunotherapy consisting of CAK cell infusion therapy following gemcitabine treatment. To investigate the underlying mechanisms by which CAK cells synergize with gemcitabine, we used enzyme-linked immunosorbent assay, Real-time reverse transcription polymerase chain reaction assay, calcein-release assay, and adherent target detachment assay. Using these assays we determined the NKG2D ligands such as major histocompatibility complex-class I-related chain (MIC)A/B expression in carcinoma cells and the level of cellular cytotoxicity generated by treatment with gemcitabine with/without CAK cells. The tumor responses differed among the patients (n=23). In vitro experiments revealed that MICA/B protein and mRNA expression were up-regulated in several carcinoma cell lines after gemcitabine treatment. Pre-treatment with gemcitabine and subsequent exposure to CAK cells induced greater cytotoxicity than either treatment alone. Inclusion of soluble MICB in CAK cell-mediated cytotoxicity assay significantly reduced cytotoxicity. Our clinical results of gemcitabine-CAK combinatorial therapy demonstrated long-term stable disease despite chemoresistance. In conclusion, the combination of gemcitabine and CAK cells may have clinical therapeutic significance for pancreatic, hepato-biliary tract, and urothelial tract cancer. Our study shows that combining CAK therapy with gemcitabine can lead to successful treatment of metastatic cancer. |
| 巻・号 | 34(8) |
| ページ | 4529-38 |
| 公開日 | 2014-8-1 |
| PII | 34/8/4529 |
| PMID | 25075096 |
| MeSH | Adult Aged Aged, 80 and over Antimetabolites, Antineoplastic / pharmacology* Cell Line, Tumor Combined Modality Therapy Cytokine-Induced Killer Cells / immunology* Cytotoxicity, Immunologic Deoxycytidine / analogs & derivatives* Deoxycytidine / pharmacology Drug Resistance, Neoplasm* Female Gemcitabine Humans Male Middle Aged NK Cell Lectin-Like Receptor Subfamily K / physiology* Neoplasm Metastasis Neoplasms / pathology Neoplasms / therapy* Retrospective Studies |
| IF | 1.994 |
| 引用数 | 25 |
| WOS 分野 | ONCOLOGY |
| 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 | 3 |
| 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 | KLM-1(RCB2138) T24 |