白细胞介素12基因疫苗治疗低负荷恶性淋巴瘤的实验研究

目的 用低负荷恶性淋巴瘤模拟微小残留病，探讨IL-12基因治疗的疗效。方法 制备IL-12基因修饰的肿瘤细胞（ex vivo疫苗）和IL-12逆转录病毒包装细胞（in vivo疫苗）两种IL-12基因疫苗，对T细胞淋巴瘤（EL4）小鼠的低负荷淋巴瘤模型进行治疗。结果 （1）两个疫苗治疗组各约50%的小鼠长期无瘤生存，而对照组小鼠全部成瘤死亡。（2）部分长期生存的小鼠能耐受大刘量野生肿瘤细胞的再次攻击。（3）形态学检查在长期生存小鼠体内未发现残留肿瘤细胞。（4）疫苗治疗组其余小鼠成瘤时间延迟、总体存活时间延长，长出现肿瘤消退和肿瘤体积一过性减小的现象和各种免疫指标的改变。结论 IL-12基因疫苗可以有效治疗小鼠低负荷的EL4淋巴瘤的模型，为IL-12基因疫苗治疗恶性淋巴瘤的进一步临床试验打下了基础。

Experimental study of interleukin-12 gene vaccines in the treatment of low-load malignant lymphoma (EL4)

OBJECTIVE: Two kinds of murine interleukin-12 (mIL-12) fusion gene vaccines were used to treat the murine low-load malignant T cell lymphoma EL4 as minimal residual disease (MRD) model. METHODS: C57BL/6 synergistical mice were subcutaneously inoculated with 1 x 10(6) wild-type (wt) EL4 tumor cells as low-load lymphoma model treated with two mIL-12 gene vaccines. Package cell line PA317/12 producing mIL-12 retrovirus (RV) was used as in vivo vaccine and EL4 tumor cells transferred with mIL-12 gene as ex vivo vaccine. RESULTS: In both mIL-12 gene vaccine-treated groups, there was no tumor growth in 50% mice 60 days after inoculation. Nine of these no tumor growth mice were re-challenged with 5 x 10(5) wt EL4 cells, and 5 of them survived without tumors in another 60 days. All control mice died with tumors within one month after inoculation. Among those developed tumors in both vaccine-treated groups, the development of tumors was delayed, the survival period prolonged (P < 0.01), and the tumors size at death smaller (P < 0.05) as compared with the controls. In the long-survived vaccine-treated mice, no residual tumor cells were found by morphological examination. CONCLUSION: Both IL-12 gene vaccines can efficiently eliminate wt EL4 MRD in C57BL/6 mice.