| 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
|
| リソース情報 |
| ヒト・動物細胞 |
KLM-1(RCB2138)
T24 |
