我们应用逆转录病毒构建了IL-12，B7-1和GM-CSF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3种表达载体分别转染EL-4胸腺瘤细胞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被排斥后，体内试验中诱发了实验动物抗EL-4/Wt的系统性、保护性免疫，51Cr释放测定中，获得一个较强的抗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依赖于CD４+，CD8+和NK细胞。用EL-4/IL-12细胞进行疫苗治疗比较用EL-4/Neo细胞能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联合比用单一的转基因细胞增强了治疗效果(P＜0005)。结论： 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亦可有一定的应用前景。

To study the vaccine potency of gene-modified tumor cells, we have constructed IL-12,B7-1 and GM-CSF express vector using retrovirus. Methods: It was transfected into EL-4 thymic lymphoma cells respectively and the effect of gene transduction on anti-tumor immunity were investigated. Results: The tumorigenicity of EL-4/IL-12 transfectant in C57BL/6 synergistical mice was decreased significantly after implanted with EL-4/IL-12 transfectant compaired with EL-4/Wt or EL-4/Neo groups (P＜001).The systemic protective immunity was induced against the challenge with EL-4/Wt (in 10/15 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 syngeneic Lewis Lung Carcinoma cells were obtained in ５１Cr release assay. In vivo depletion analysis suggested that the decrcased tumorigenicity mainly depended on CD4＋,CD8＋ and NK cells. Therapeutic vaccines with EL-4/IL-12 cells could retard the growth to estabished EL-4/Wt tumors significantly compared with those of EL-4/Neo (P＜0005)， combination of therapeutic vaccines of EL-4/IL-12 and EL-4/B7-1 result in the enhanced the therapeutic effect of each single transficants (P＜0005) in this experimental model. Conclution: These studies suggested that immunogene treatment using IL-12 is effective in hematopoietic malignancy,and combination of IL-12 with B7-1 have a aplication value in human cancer treatment in the near future.

R730.51

* 黑龙江省自然科学基金(D9518)资助