Fundamental Study of Gene Therapy for Renal Cell Carcinoma Using IL-12

白细胞介素-12（IL-12）是一种具有抗肿瘤作用的细胞因子。为探讨IL-12基因治疗肾癌的可行性，我们利用MFG逆转录病毒载体制备了分泌IL-12的基因工程小鼠肾癌细胞。Renca IL-12可分泌146.7ng/ml/1 × 10^6细胞/48小时的活性IL-12，其体内致瘤性较Renca wild和lac Z明显降低，而体外生长和表面抗原（如MHC I类、II类或B7-1）无明显变化。结果提示，局部高浓度IL-12诱导的抗肿瘤免疫反应可能是Renca IL-12致瘤性丧失的原因。Renca IL-12还在远处抑制Renca wild的生长。此外，一些被排斥的接种Renca IL-12的小鼠被确定为对Renca wild的再攻击具有免疫力。我们认为这些结果支持IL-12基因治疗肾癌的可行性。

Interleukin-12 (IL-12) is expected a cytokine which can induce a potent antitumor effect. To determine the possibility of IL-12 for gene therapy of renal cell carcinoma, we prepared genetically engineered murine renal cell carcinoma to secrete IL-12 using MFG retroviral vector. Renca IL-12 can secrete 146.7ng of bioactive IL-12/ml/1x10^6cell/48 hr. In vivo tumorigenecity of Renca IL-12 reduced significantly compared with Renca wild and lac Z,whereas in vitro growth and surface antigen, such as MHC class I,class II,or B7-1, of each cells did not alter. These results suggested that antitumor immune response induced by high concentration of IL-12 in local site might be responsible for loss of tumorigenecity of Renca IL-12. Renca IL-12 also inhibited the growth of Renca wild at a distant site. Furthermore, some mice rejected inoculated Renca IL-12 were determined to be immune to a rechallenge of Renca wild. We believe that these results support the feasibility of IL-12 gene therapy for the treatment of renal cell carcinoma.