The impact of intraoperative vaccination with IL-12 modified autologous tumor cells in the Lewis lung carcinoma mouse model

To improve immunological defense of tumors, we investigated the effect of intraoperative vaccination with IL-12 cDNA transfected cells in an autologous mouse tumor model. Tumors derived from autologous Lewis lung carcinoma cells were established in C57/BL6 mice. At day seven, the tumors were surgically removed. Simultaneously, the mice were vaccinated intraoperatively with Lewis lung carcinoma cells transfected with an IL-12-encoding pRSC construct or with the empty plasmid, or with dead cells either intrasplenically (i.s.) or subcutaneously (s.c.). Control mice did not obtain vaccination. Tumor re-growth, survival, and metastasis were monitored. Mice with no tumor re-growth underwent a second tumor implantation. The same parameters were examined. After tumor resection and vaccination tumors reappeared in 60.0% of the animals of the control group. Lowest tumor reoccurrence rates of 41.4 and 43.5% were seen in animals receiving IL-12 pRSC cells either i.s. or s.c. Survival tended to be enhanced in all vaccinated animals compared with the control group. Following R0 tumor resection, the rate of tumor-free survivors was highest when IL-12 pRSC cells were given i.s. (73%, control 45%). 37-59% of the mice of the therapy groups did not develop a tumor, that is, they were tumor-free survivors. These mice underwent a second tumor implantation 120 days after tumor resection and vaccination. Tumor growth was significantly delayed in mice receiving IL-12 pRSC cells. Intraoperative autologous whole-cell vaccination is practicable and proved to have anti-tumor potential, and therefore, it could be an additional option in adjuvant cancer therapy.