过继回输腺病毒介导的白细胞介素10基因转染CTL对机体抗肿瘤免疫功能的增强效应(英文)

Enhanced Antitumor Effect by Adoptive Transfer of Cytotxic T Lymphocytes Producing Interleukin-10 by Adenovirus-Mediated Gene Transduction

本研究探讨了白细胞介素10(IL-10)对小鼠体内抗肿瘤免疫功能的影响。鉴于C26结肠癌细胞转染了IL-10基因后在体内的致瘤性明显下降,本研究构建了一株对C26结肠癌细胞具有杀伤活性的CD8^+CTL并观察了IL-10基因转染的该细胞株对肿瘤的治疗作用。携带IL-10基因的重组腺病毒能有效介导小鼠淋巴细胞的基因转染并使之分泌较高水平的IL-10。IL-10基因转染的CTL过继回输荷瘤小鼠体内能明显增强荷瘤小鼠的体内抗肿瘤免疫功能,使实验性肺转移小鼠肺部转移结节数明显减少,这表明,IL-10对于过继回输的肿瘤特异性CTL的免疫功能具有明显的增强作用。

In vivo effects of IL-10 on host antitumor immunity were tested in murine tumor models. Gene transduction of Colon 26 cells with murine IL-10 gene resulted in a marked decrease of tumorigenicity in vivo. A cell line of CD8-positive cytotoxic T lymphocytes (CD8 +CTL) with strong cytolytic activity against Colon 26 wasestablished , and therapeutic effect of IL-10 gene introduction into the CD8+CTL was studied. A recombinant adenovirus Adexl CAmILl0 enabled us to achieve very efficient gene transduction and high level production of IL-10 in murine lymphocytes. IL-10 gene - transduction of CTL exerted an increased antitumor response in the adoptive treatment models, resulting in markedly reduced numbers of metastatic nodules in the lung. Our findings indicate that IL - 10 works as an immunostimulator in the adoptive transfer therapy with tumor - specific CTL.