细胞因子处理联合B7—l基因转染制备有效的肝癌疫苗

Effective Hepatoma Vaccine Made by Cytokines Combined with B7-1 Gene Transfection

在体外用IFN-Y和TNF-。等细胞因子处理B7-1表达阳性的Hepal-6,观察其对小鼠肝癌表面MHC Class Ⅰ和ICAM-1表达的调节作用和对体内外抗肿瘤免疫反应的影响。结果发现:单独B7-1基因转染的Hepal-6的致瘤性消失,但仅能诱导部分细胞毒性和部分保护性免疫反应,而B7-1基因转染与细胞因子处理联合应用则能诱导强烈的细胞毒杀伤活性和完全的抗Hepal-6保护性免疫反应。结论B7-1共刺激分子在小鼠肝癌的表达是激活抗肿瘤免疫所必需的但不充分,而B7基因转染联合IFN-7等细胞因子处理能诱导彻底的抗肿瘤免疫反应。

To study the effects of cytokines treatment combined with B7-1 gene transfection on expression of MHC class I and ICAM-1 and regulation of antitumor immune response, iFN-γ and TNF-α were added into murine hepatoma Hepal-6 cell line transfected with B7-1 gene. Results show that in contrast to the lethal growth of the parental Hepal-6 tumor, B7-l-positive Hepal-6 regressed when inoculated into syngeneic mice. Moreover, B7-l-positive or cytokine treated Hepal-6 alone only induce low CTL activity and partial protection against the challenge of Hepal-6 tumor; in contrast, B7-l-positive Hepal-6 with treatment of cytokines effectively stimulated spleen cells with generation of high CTLs activity and provide parental cell complete protection. It suggests that expression of costimulatory factor B7-1 is necessary but not efficient in inducing anti-hepatoma immunity, while B7-1 combined with IFN-γ and TNF-α induced complete immune response in murine hepatoma model.