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

Gene Ther. 1999 May;6(5):833-9. doi: 10.1038/sj.gt.3300891.

Abstract

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 +/- 82 pg/mg) from explanted tumors in culture supernatants. Treated tumors showed increased infiltration of NK, CD4+ and CD8+ T cells and up-regulation of MHC class I 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 micrograms, 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 effectors. 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 established tumors.

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • Carcinoma, Renal Cell / immunology
  • Carcinoma, Renal Cell / therapy*
  • Colonic Neoplasms / immunology
  • Colonic Neoplasms / therapy*
  • Female
  • Gene Expression
  • Genetic Therapy / methods*
  • Genetic Vectors
  • Immunotherapy, Active / methods*
  • Injections, Intralesional
  • Interferon-gamma / genetics
  • Interleukin-12 / genetics*
  • Kidney Neoplasms / immunology
  • Kidney Neoplasms / therapy*
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms, Experimental / immunology
  • Neoplasms, Experimental / therapy
  • Tumor Cells, Cultured

Substances

  • Interleukin-12
  • Interferon-gamma