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 +/- 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.
Mendiratta
S K
SK
GeneMedicine, Inc. The Woodlands, TX 77381-4248, USA.
Quezada
A
A
Matar
M
M
Wang
J
J
Hebel
H L
HL
Long
S
S
Nordstrom
J L
JL
Pericle
F
F
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000628:therapy*; D003110:Colonic Neoplasms / Q000276:immunology / Q000628:therapy*; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D016233:Immunotherapy, Active / Q000379:methods*; D015552:Injections, Intralesional; D007371:Interferon-gamma / Q000235:genetics; D018664:Interleukin-12 / Q000235:genetics*; D007680:Kidney Neoplasms / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy; D014407:Tumor Cells, Cultured
D018664:Interleukin-12; D007371:Interferon-gamma