B7基因转导非免疫原性肿瘤B16并联合应用IFN-γ的抗肿瘤研究

目的探索非免疫原性肿瘤的免疫基因治疗。方法将Ｂ７１基因导入非免疫原性肿瘤细胞Ｂ１６,在体外经ＩＦＮγ处理后,观察细胞表面分子的表达变化,以及肿瘤细胞在小鼠体内的成瘤性。结果单独Ｂ７基因转导的Ｂ７＋Ｂ１６在小鼠体内持续生长。体外用ＩＦＮγ处理肿瘤细胞,可明显增加细胞表面ＭＨＣＩ类分子的表达,与Ｂ７－Ｂ１６比较,Ｂ７＋Ｂ１６在小鼠体内的成瘤性明显降低。结论单独Ｂ７基因导入并表达,不能改变Ｂ１６在体内恶性增殖的特性。同时提高细胞表面Ｂ７与ＭＨＣＩ分子的表达,两者可协同发挥作用,诱发肿瘤排斥。

Rejection of non-immunogenic tumor cells transfected with costimulatory molecule B7 after treatment with IFN-gamma in vitro

OBJECTIVE: To explore immuno-gene-therapy of non-immunogenic tumor. METHODS: Non-immurogenic tumor cells B16 were transfected with B7-1 gene. The B7-1 gene transfected B16 cells (B7+ B16) were treated with recombinant murine interferon-gamma (rmIFN-gamma) in vitro, and then inoculated to C57BL/6 mice. RESULTS: While B7+ B16 cells grew progressively in syngeneic mice, tumorigenicty was significantly reduced when B7+ B16 cells were treated with rmIFN-gamma before inoculation to mice. Flow cytometric analysis of the rmIFN-gamma treated B7+ B16 cells showed significant up-regulation of MHC class I expression. CONCLUSION: For non-immunogenic tumor if the expressions of MHC class I molecules is low, providing co-stimulatory molecule B7 is not enough to reduce tumorigenicity. The B7-1 gene transfected B16 cells become non-tumorigenic or weakly tumorigenic when their MHC class I is up-regulated.