插入外源性白细胞介素2基因的肿瘤细胞的抗肿瘤抗转移作用

Anti-tumor and Anti-metastasis Effects of Tumor Cells Transduced with the Gene, Cording for Human Interleukin-2

我们应用逆转录病毒载体pLXSN将人IL-2基因插入大鼠和人的肿瘤细胞.探讨了携带外源性IL-2基因的肿瘤细胞的体内外生物学特性及其意义.转基因细胞在体外培养中的细胞形态、生长特性以及软琼脂集落形成能力未见明显改变,但对杀伤性免疫活性细胞的杀伤更为敏感,与淋巴细胞混合培养的上清中测得更高水平的IFN和TNF活性.大鼠肿瘤细胞WBT插入IL-2基因后,其体内成瘤性明显下降.腹腔接种WBT/IL-2细胞可使大鼠获得抗肿瘤免疫能力以抑制皮下野生型WBT细胞的生长.携带IL-2基因的人和大鼠肿瘤细胞在裸鼠体内可以成瘤,但生长缓慢.具有高转移能力的Anip973细胞插入IL-2基因后,在裸鼠体内的转移性丧失.结果提示IL-2基因插入肿瘤细胞进行肿瘤基因治疗的有效性、可行性和发展潜能.

Reccent investigations demonstrated that genetically modified tumor cells could be used as vaccines against cancer. In this light, we introduced human interleukin -2 (IL-2) gene into a poorly immunogenic rat fibrosarcoma cell line WBT, a human lung abenocarcinoma cell line AGZY and a highly metastatie sub - cell line Anip973 derived from AGZY. The transduced cells showed no obvious changes in morphology, growth and colony - forming ability in soft agar.Transduction with IL-2 gene rendered the cells more sensitive than the parental cells and cells transduced with NeoR gene alone to the lysis by cytotoxic lymphocytes. High levels of IFN and TNF were detected in the supernatants of cocultured lymphocytes and tumor cells containing IL-2 gene. Tumorigenicity of WBT/IL-2 cells was greatly reduced in syngeneic rats. Metastatic capacity of Anip973 in nude mice was blocked by the transduction of IL-2 gene, but not the transduction of NeoR gene alone. Inoculation of WBT/IL-2 cells conferred rats resistance to the challenge of parental WBT cells.Splenocytes from WBT/IL-2-inoculated rats restimulated with WBT cells in vitro showed high CTL activity against WBT cells. Our results demonstrated the potential application of tumor cells transduced with IL— gene as active vaccine against cancer.