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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 construct IL-12 and B7-1 expression vectors using retroviruses to study the role of cancer vaccines in genetically modified tumor cells. METHODS: Two kinds of expression vectors were transfected into EL-4 thymoma cells respectively, so that the cells could express and secrete B7-1 or IL-12, and the anti-tumor immunity effect of the gene into the cells was studied. RESULTS: After inoculation of EL-4/IL-12 transfected cells, the tumorigenicity of the gene-introduced cells in C57BL/6 syngeneic mice was significantly reduced compared to the EL-4/Wt and EL-4/Neo groups (P< 0.01). After the tumor in the EL-4/IL-12 group was rejected, the experimental animals induced systemic and protective immunity against EL-4/Wt. The 51Cr release assay proved to be a strong one. Anti-EL-4/Wt and a weaker CTL activity against syngeneic Lewis tumor cells, the results of in vivo lymphocyte depletion assays suggest that reduced tumorgenicity is mainly associated with CD4+, CD8+, and NK cells. Vaccine treatment with tumor cells transfected with the EL-4/IL-12 gene was more effective in delaying the growth of established EL-4/Wt tumors compared with vaccines treated with EL-4/Neo tumor cells (P<0. 005) The combined treatment of EL-4/IL-12 and EL-4/B7-1 genes enhanced the therapeutic effect compared with single transgenic cells (P < 0.005). Conclusion: The results suggest that the use of IL-12 for the treatment of hematological neoplasms is effective, and the combined use of IL-12 and B7-1 has a certain application prospect in the treatment of future human cancers.