Intraoperative subcutaneous or intrasplenic vaccination with modified autologous tumor cells leads to enhanced survival in a mouse tumor model.

PURPOSE: We investigated the effect of intraoperative intrasplenic or subcutaneous vaccination with modified tumor cells on tumor progression in a mouse model. METHODS: Pre-established B16 melanomas on C57/Bl6 mice were surgically removed; mice were vaccinated intraoperatively with B16 cells transfected with an IL-12-encoding pRSC construct, the empty plasmid, or B16 frozen cells. Cells were given either intrasplenically or subcutaneously. Intrasplenic effects of vaccination were examined along with survival data. Mice without tumor recurrence underwent a second tumor implantation. RESULTS: Animals administered IL-12 pRSC cells showed significant alterations in the spleen, such as higher percentages of (activated) CD4+ and CD8+ T cells and tumor-specific CD4+ T cells among splenocytes. The tumor recurrence rate after resection ranged from 13 to 36%. Cases with recurrent tumors in particular benefited in all therapy groups, resulting in enhanced (tumor-free) survival, reduced tumor growth and lower metastasis rates. Following macroscopic complete tumor resection, the optimum outcome resulted from vaccination with IL-12 pRSC cells into the spleen and subcutaneously administered frozen cells. Survival times were enhanced in all therapy groups after tumor reimplantation, although results were not significant. CONCLUSIONS: Intraoperative whole-cell vaccination with autologous tumor cells yields promising data, and could be considered as a future option in adjuvant cancer therapy.

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

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.