Combined CXC chemokine and interleukin-12 gene transfer enhances antitumorimmunity

It has been shown that intratumor administration of an adenovirus vector ex pressing IL-12 produces a potent T cell-mediated response that leads to sig nificant tumor regression in a murine breast cancer model. IP-10 and MIG ar e CXC chemokines that recruit mononuclear cells in vivo. In addition to the ir chemotactic roles, IP-10 and MIG inhibit angiogenesis, We tested whether the addition of IP-10 or MIG may both enhance the antitumor immune respons e of IL-12 through T cell recruitment and inhibit tumor growth through angi ostasis. Adenovirus vectors expressing IP-10 or MIG and/or IL-12 were admin istered intratumorally in a murine model of mammary adenocarcinoma and fibr osarcoma. Administration of IP-10 or MIG in combination with IL-12 resulted in considerable tumor regression and increased survival time of tumor-bear ing animals as compared with IP-10, MIG, IL-12 alone or control-treated ani mals, with the IP-10 IL-12 combination being most effective. These results suggest augmenting the antitumor immune response and inhibiting tumor angio genesis with adenoviral vectors expressing IP-10 in combination with IL-12 is a novel way to enhance tumor regression.