共刺激信号B7—1表达对小鼠肿瘤细胞生长和转移的影响

为Ｂ７１分子基因在肿瘤免疫基因治疗中的应用提供实验依据。方法通过逆转录病毒介导的基因转移技术，将Ｂ７１ｃＤＮＡ导入具有不同免疫原性的小鼠肿瘤细胞获得表达，并观察转基因细胞在纯系小鼠体内生长和转移的改变。结果由于Ｂ７－１基因的转导表达，使具有免疫原性的ＥＬ４Ｔ淋巴瘤细胞致瘤性丧失；使非免疫原性的Ｂ１６黑色素瘤、Ｐ８１５肥大细胞瘤和ＭＡ８９１乳腺癌细胞的致瘤性减弱；使Ｂ１６细胞的实验性转移和ＭＡ８９１细胞的自发肺转移能力降低。通过转导Ｂ７－１基因的Ｂ１６细胞的免疫接种，可使再次接种的亲本Ｂ１６细胞的致瘤性减弱：但对已生长的亲本Ｂ１６细胞影响不明显。结论Ｂ７１基因导入不同的肿瘤细胞后，可引起机体产生不同程度抗肿瘤免疫反应，使肿瘤细胞在体内的生长和转移能力丧失或减弱，这种反应的强弱与肿瘤细胞本身的特性有关。

Abrogated or decreased tumorigenicity and metastasis induced by retroviral mediated B7.1 gene transfer on marine tumors with different immunogenicity

Objective To investigate the differences of tumorigenicity and metastasis of murine tumors with different immunogenicity by B7.1gene transfer.Method Using retroviral-mediated gene transfer,we transduced B7.1cDNA into a panel of murine tumor lines with different immunogenicity to study the ef fect of B7.1 costimulation on antitumor immunity.Results After transduced with B7.1 cDNA.the immunogenic T lymphoma EL4 regressed completely,and tumorgenicity of three nonimmunogenic tu mors melanoma B16,mastocytoma P815 and mammary adenocarcinoma MA891 were significantly re duced in syngeneic mice.The experimental metastasis of B16 and spontaneous pulmonary metastasis of MA891 were profoundly suppressed.Moreover,immunization with B7.1 cDNA transduced B16 in duced systemic immunity against subsequently inoculated parental B16 tumor,while this immunization method did not provide protective immunity against established parental B16 tumor.Conclusion Our results show that varied extent of antitumor immunity can be induced to abrogate or decrease tumori genecity and metastasis through B7.1 gene transduction,depending on the immunogenic potential of tu mors.