Interleukin-15-transferred cytokine-induced killer cells elevated anti-tumor activity in a gastric tumor-bearing nude mice model.
Gastric cancer is the second leading cause of cancer-related mortality worldwide. Adoptive cell therapy (ACT) for gastric cancer is a novel therapy modality. However, the therapeutic effectiveness in vivo is still limited. The objective of this study was to assess the value of interleukin-15 (IL-15)-transferred cytokine-induced killer (CIK) cells in ACT for gastric cancer. IL-15-IRES-TK retroviral vector was constructed and transferred into the CIK cells. A gastric tumor-bearing nude mice model was constructed by subcutaneously injecting gastric cancer cells, BGC-823. Gastric tumor-bearing nude mice were randomly divided into three groups (five mice each group) and injected with physiological saline, CIK cells, and IL-15-IRES-TK-transfected CIK cells for 2 weeks, respectively. IL-15-IRES-TK-transferred CIK cells were prepared successfully and flow cytometry (FCM) analysis indicated that the transfection rate reached 85.7% after 5 days culture. In vivo experiment, we found that CIK cells retarded tumor growth by reducing tumor volume and tumor weight, as well as increasing tumor inhibition rate. Furthermore, IL-15-IRES-TK-transferred CIK cells showed a much stronger inhibition on tumor growth than CIK cells alone. Tumor morphology observation and growth indexes also showed that IL-15-transfected CIK cells had stronger cytotoxicity to tumor tissue than CIK cells. IL-15-IRES-TK transfection could elevate the effects of CIK cells to gastric carcinoma. The engineered CIK cells carrying IL-15-IRES-TK may be used in the ACT for gastric carcinoma, but prudent clinical trial is still indispensable.
Department of General Surgery, Chinese PLA General Hospital, Beijing, 100853, China.
Zheng
Z
Peng
Institute of General Surgery, Chinese PLA General Hospital, Beijing, 100853, China.
Wentao
W
Liang
Institute of General Surgery, Chinese PLA General Hospital, Beijing, 100853, China.
Zexue
Z
Li
Institute of General Surgery, Chinese PLA General Hospital, Beijing, 100853, China.
Yingxin
Y
Xu
Department of General Surgery, Chinese PLA General Hospital, Beijing, 100853, China.
Lin
L
Chen
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000276:immunology; D045744:Cell Line, Tumor; D055612:Cytokine-Induced Killer Cells / Q000187:drug effects; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D019409:Interleukin-15 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D055611:Natural Killer T-Cells / Q000276:immunology*; D011897:Random Allocation; D013274:Stomach Neoplasms / Q000276:immunology / Q000628:therapy*; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D019409:Interleukin-15
anti-tumor; cytokine-induced killer cells; gastric cancer; interleukin-15; tumor-bearing nude mice model