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) ge ne delivery system to deliver IL-12 to two different types of murine tumors , an immunogenic renal cell carcinoma, Renca, and a non-immunogenic colon c ell carcinoma, CT26. The delivery of IL-12/polyvinyl pyrrolidone (PVP) comp lexes 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. Trea ted tumors showed increased infiltration Of NK, CD4(+) and CD8(+) T cells a nd 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, re spectively While polymorphonuclear cells (PMNs) were partially involved in the development of the antitumor immune response elicited by IL-12/PVP trea tment, 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 developme nt of tumor specific immunity. Finally, mice that rejected the tumors follo wing IL-12/PVP treatment were protected against a second challenge with the same tumor. These data provide evidence that a nonviral IL-12 gene deliver y system is well tolerated and generates a potent immune response against T established tumors.