Using three murine
tumor models, we compared the antitumor efficacy and certain physiological effects of an in vivo
interleukin-12 (IL-12) gene therapy protocol and a systemic
IL-12 protein therapy protocol. An
IL-12 cDNA gene construct was administered in situ into skin tissue via gene gun delivery, and recombinant
IL-12 protein was administered subcutaneously at a dose of 1 microgram/mouse/treatment. Both treatment regimes induced a comparable level of regression of established intradermal MethA
sarcomas. In
B16 melanoma and P815
mastocytoma models, antitumor efficacy of
IL-12 protein therapy appeared to be slightly higher than that of
IL-12 gene therapy; however, the
protein therapy protocol in this comparative study resulted in a high level of mortality of mice. It was also demonstrated that
IL-12 gene therapy, in contrast to the
IL-12 protein therapy, was not associated with
weight loss,
splenomegaly, increased Ly6
antigen expression in the spleen, or visible signs of toxicity, such as fur ruffling and
lethargy. Moreover, serum levels of
interferon-gamma (IFN-gamma) induced in response to
IL-12 gene therapy were 300-1000 times lower than those induced by the systemic
IL-12 protein administration. Together, these results suggest that gene gunmediated in vivo delivery of
IL-12 cDNA may be considered as a safer alternative to
IL-12 protein therapy for certain human
cancers.