IL-12协同B7-1转基因细胞增强C57BL/6小鼠的抗肿瘤免疫

Synergism of Il－12 and B7－1 Transfectants May Enahance the Antitumor Immunity in C57BL／6 Mice

目的：应用逆转录病毒构建IL－12、B7－1表达载体，以研究基因修饰的肿瘤细胞的癌疫苗作用。方法：将两种表达载体分别转染EL－4胸腺瘤细胞，使该细胞能表达分泌B7－1或IL－12，并研究了该基因导入细胞的抗肿瘤免疫效果。结果：当接种了EL－4／IL－12转染细胞后，在C57BL／6同系鼠中其基因导入细胞的肿瘤原性比较EL－4／Wt和EL－4／Neo组明显减少（P＜0．01），在EL－4／IL－12组的肿瘤被排斥后，实验动物体内诱发了抗EL－4／Wt的全身性、保护性免疫，用51Cr释放测定法证明有一个较强的抗EL－4／Wt和一个较弱的抗同系Lewis肿瘤细胞的CTL活性，体内淋巴细胞消除分析的结果提示减少的肿瘤原性主要与CD4＋、CD8＋和NK细胞有关。用EL－4／IL－12基因转染的瘤细胞进行疫苗治疗比较用EL－4／Neo瘤细胞作疫苗治疗能更加有效地延缓已建立的EL－4／Wt肿瘤的生长（P＜0．005），EL－4／IL－12和EL－4／B7－1基因联合转染组比用单一的转基因细胞增强了治疗效果（P＜0．005）。结论：研究结果提示应用IL－12进行血液肿瘤的治疗是有效的，IL－12和B7－1联合使用在未来人类癌症的治疗中有一定的应用前景。

Objective： To study the vaccine potency of gene－modified tumor cells， we have constructed IL－12， B7－1 expression vector using retrovirus． Methods： The two expression vectors were transfected into EL－4 thymic lymphoma cells and the effect of gene transduction on antitumor immunity were studied． Results： The tumorigenicity of EL－4／IL－12 transfectant in C57BL／6 synergisstical mice decreased significantly after implantation of EL－4／IL－12 transfectant as compaired with EL－4／Wt or EL－4／Neo groups（P＜0．01）． The systemic protective immunity was induced against the chanllenge with EL－4／Wt （in10／15 mice） after the rejection of EL－4／IL－12． In vivo experiment， a stronger CTL activity against EL－4／Wt cells and a weak killer activity against synergeneic Lewis lung carcinoma cells were obtained in 51Cr release assay． In vivo， the depletion analysis suggested that the decreased tumorigenicity mainly depended on CD4＋， CD8＋ and NK cells． Therapeutic vaccines with EL－4／IL－12 cells could retard the growth of established EL－4／Wt tumors significantly as compaired with those of EL－4／Neo （P＜0．005）． Combination use of the therapeutic vaccines of EL－4／IL－12 and EL－4／B7－1 resulted in enhancing the therapeutic effect of each single transfectant in this experimental model （P＜0．005）． Conclusion： These studies suggested that immune treatment using IL－12 is effective in hematopoietic malignancy， and conbination of IL－12 and B7－1 may be of value in human cancer treatment．