白细胞介-素12基因invivo疫苗治疗恶性淋巴瘤的实验研究

THERAPEUTIC EFFECTS OF INTERLEUKIN-12 GENE in vivo VACCINE FOR MURINE T CELL LYMPHOMA (EL4) IN C57BL/6 MICE

作者制备了IL 12基因的invivo包装细胞疫苗 ,对T细胞淋巴瘤 (EL4 )的小鼠肿瘤模型进行治疗。将C5 7BL/ 6小鼠分为4组 ,除阴性对照组外 ,其余 3组小鼠先于左侧背部皮下接种野生性EL4细胞 1× 10 6/只 ,此后第 1、7、14、2 1天分别于接种肿瘤的部位皮下注射经60 Co照射的invivo疫苗PA317/ 12、60 Co照射的NeoR空载体对照细胞PA317/N(各 1× 10 7细胞 /只)或PBS。结果显示 ,①invi vo疫苗组最终 5只(5 0 % )小鼠长期无瘤生存 ,其中 3只曾触及一过性的肿瘤结节 ,而阳性对照和NeoR空载体组的小鼠在 1个月内全部成瘤死亡 ;②部分 (3/ 5 )长期生存的invivo疫苗组小鼠能耐受野生肿瘤细胞的再次攻击 ;③invivo疫苗组形成肿瘤小鼠也有成瘤时间延迟、存活时间延长和肿瘤体积短暂减小的现象等 ,显示了疫苗治疗的疗效 ;④病理检查发现invivo疫苗组小鼠形成的肿瘤具有较完整的包膜 ,内部有大量的淋巴细胞浸润 ,血供较差等。长期生存小鼠体内未发现残留肿瘤细胞 ,而长期生存小鼠的脾细胞杀肿瘤活性明显增强。这些结果提示 ,IL 12的invivo包装疫苗可以有效治疗EL4小鼠的淋巴瘤模型 ,为IL

C57BL/6 synergistical mice were divided into 4 groups (10 mice each). The first group was negative control without any interference. Each mouse in the other 3 groups was subcutaneously inoculated with 1 10 6 wide type (wt) EL4 tumor cells. Then each group was treated either with interleukin 12 (mIL 12) in vivo vaccine or NeoR control vaccine or PBS(positive control group) on day 1, 7, 14, 21, on the same place where wt EL4 tumor was inoculated. mIL 12 in vivo vaccine and NeoR control vaccine were package cells which can produce retrovirus (RV) with mIL 12 or NeoR gene, the vaccine was 60 Co irradiated and injected (1×10 7 cells/mouse). All mice in positive group and NeoR control group died of tumors in a month, while 5/10 mice in mIL 12 in vivo vaccine groups survived without tumors for more than 60 days. The 5 survived mice were rechallenged with 5×10 5 wt EL4 cells, 3/5 mice even survived without tumors for another 60 days. Among the mice with tumors in vivo vaccine group mice, compared with the controls, the development of tumors was delayed ( P <0 01), and the survival period was prolonged ( P <0 01), and tumors were smaller ( P <0 05) and there were more lymphocytes infiltrated within the tumors. No residual tumor cells were found in long survival mice by morphological examination. These results suggest that mIL 12 in vivo vaccine can efficiently eliminate wt EL4 in C57BL/6 mice.