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[成纤维细胞介导的白细胞介素-2基因治疗增强免疫功能及抗肿瘤活性]

[Enhanced immune functions and antitumor activity of fibroblast-mediated interleukin-2 gene therapy].

作者信息

Cao X T, Zhang W P, Tao Q

机构信息

Department of Immunology, Second Military Medical University, Shanghai.

出版信息

Zhonghua Yi Xue Za Zhi. 1995 Sep;75(9):521-4, 573.

PMID:8556540
Abstract

The aim of the present study was to establish fibroblastmediated IL-2 gene therapy and to observe its antitumor effect in the mouse tumor model. The IL-2 gene-transfected fibroblasts (NIH3T3-IL-2+) secreting high level of IL-2 were encapsulated with collagen and then implanted i.p. into mice. Certain level of IL-2 could be detected in murine serum for some periods, and the splenic proliferation, NK and LAK activities, cytokine production (IFN-v, TNF, IL-2) were enhanced significantly. It was of great importance that the high endogenous LAK activity was induced. The significant therapeutic effect of i.p. implantation of NIH3T3-IL-2+ on ascitic liver carcinoma-bearing mice was observed. The better therapeutic results could be achieved. NIH3T3-IL-2+ cells were i.p. implanted in combination with i.p. injection of LAK cells. These results demonstrated that fibroblast--mediated IL-2 gene therapy has potent antitumor effect via augmentation of immune functions and the antitumor effect will be more obvious when IL-2 gene therapy is used along with the adoptive transfer of LAK cells.

摘要

本研究的目的是建立成纤维细胞介导的白细胞介素-2(IL-2)基因治疗方法,并观察其在小鼠肿瘤模型中的抗肿瘤作用。将分泌高水平IL-2的IL-2基因转染的成纤维细胞(NIH3T3-IL-2+)用胶原蛋白包裹,然后腹腔注射到小鼠体内。在一段时间内可在小鼠血清中检测到一定水平的IL-2,并且脾细胞增殖、自然杀伤(NK)和淋巴因子激活的杀伤细胞(LAK)活性、细胞因子产生(干扰素-γ、肿瘤坏死因子、IL-2)均显著增强。诱导出高内源性LAK活性具有重要意义。观察到腹腔注射NIH3T3-IL-2+对荷腹水型肝癌小鼠具有显著的治疗效果。可以取得更好的治疗结果。将NIH3T3-IL-2+细胞腹腔注射与LAK细胞腹腔注射联合应用。这些结果表明,成纤维细胞介导的IL-2基因治疗通过增强免疫功能具有强大的抗肿瘤作用,并且当IL-2基因治疗与LAK细胞的过继性转移联合使用时,抗肿瘤作用将更加明显。

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