Intratumoral delivery of IL-12 gene by polyvinyl polymeric vector system to murine renal and colon carcinoma results in potent antitumor immunity

We have utilized a nonviral, polymeric interactive non-condensing (PINC) gene delivery system to deliver IL-12 to two different types of murine tumors, an immunogenic renal cell carcinoma, Renca, and a non-immunogenic colon cell carcinoma, CT26. The delivery of IL-12/polyvinyl pyrrolidone (PVP) complexes into Renca led to the expression of IL-12 (146 +/- 89 pg/mg) and iFN-gamma (160 +/- 82pg/mg) from explanted tumors in culture supernatants. Treated tumors showed increased infiltration Of NK, CD4(+) and CD8(+) T cells and up-regulation of MHC 1 molecules on leukocytes in both tumors and lymph, nodes. Fifty per cent of tumor-bearing mice rejected Renca or CT26 tumors following IL-12/PVP treatments given at optimal doses of 24 and 48 mu g, respectively While polymorphonuclear cells (PMNs) were partially involved in the development of the antitumor immune response elicited by IL-12/PVP treatment, CD8(+) T cells were found to be the primary effecters. in contrast, CD4(+) T cells did not appear : to play a significant role in the development of tumor specific immunity. Finally, mice that rejected the tumors following IL-12/PVP treatment were protected against a second challenge with the same tumor. These data provide evidence that a nonviral IL-12 gene delivery system is well tolerated and generates a potent immune response against T established tumors.