成纤维细胞介导的白细胞介素2基因疗法的免疫增强作用及其抗肿瘤效果

为了使白细胞介素２（ＩＬ－２）在体内持续有效地发挥生物学效应，作者探讨了成纤维细胞为介导途径的ＩＬ－２基因疗法以及该疗法在小鼠体内的抗肿瘤作用。将基因转染后、高分泌ＩＬ－２的成纤维细胞（ＮＩＨ３Ｔ３－ＩＬ－２＋）包裹入胶原后移植入小鼠腹腔内，可使小鼠血清中持续性地存在一定水平的ＩＬ－２，并能非常显著地增强小鼠脾细胞的增殖反应、天然杀伤细胞（ＮＫ）活性和淋巴因子激活的杀伤细胞（ＬＡＫ）活性、分泌细胞因子（ＩＦＮ－γ、ＴＮＦ、ＩＬ－２）的水平，尤其有意义的是诱导出内源性的ＬＡＫ活性。ＮＩＨ３Ｔ３－ＩＬ－２＋腹腔内移植后对腹水型肝癌小鼠有较显著的治疗效果，当与ＬＡＫ细胞腹腔内注射联合应用后，治疗效果更佳，表明成纤维细胞介导的ＩＬ－２基因疗法能通过增强机体的免疫功能发挥显著的抗肿瘤作用，而且当其与ＬＡＫ细胞过继回输合用后抗肿瘤作用更强。

Enhanced immune functions and antitumor activity offibroblastmediated IL-2 gene therapy

he aim of the present study was to establish fi-broblastmediated IL-2 gene therapy and to observe itsantitumor effect in the mouse tumor model. The IL-2gene-thansfected fibroblasts (NIH3T3-IL-2 ) secret-ing high level of IL-2 were encapsulated with collagenand 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 prodution (IFN-v, TNF, IL-2) were en-hanced significantly. It was of great importance thatthe high endogenous LAK activrty was induced. Thesignificant therapeutic effect of i. p. implantation ofNIH3T3-IL-2 Qn ascitic liver carcinoma-bearing micewas observed. The better therapeutic results could beachieved. NIH3T3-IL-2 cells were i. p. implanted incombination with i. p. injection of LAK cells. Theseresults demonstrated that fibroblast mediated IL-2gene therapy has potent antitumor effect via augmentation of immune functions and the antitumor effect willbe more obvious when IL-2 gene therapy is used alongwith the adoptive transfer of LAK cells.