Chemokines Transgene Induces Antitumor Immunity Through Chemoattraction And Activation Of Dendritic Cells

Chemokine gene transfection represents a promising approach in the treatment of malignancies. The CC chemokine macrophage-derived chemokine(MDC), which can chemoattract (dendritic cell)DC, NK cells and Th2 T cells, was transfected in vivo to investigate its efficacy of antitumor response and the role of antitumor immunity playing in the course. We observed that intratumoral injection of AdMDC resulted in a markedly tumor regression in preestablished murine subcutaneous 3LL carcinoma and induced significant CTL activity. The antitumor response was demonstrated to be CD4+ T cell- and CD8+ T cell-dependent. After MDC administration DC could be chemoattracted to the tumor site, facilitated to migrate to draining lymph or spleen, and finally activated to produce a high level of IL-12.Furthermore, a significant increase of IL-4 production was found within the tumors at early time after the AdMDC administration and followed by the increase of IL-12 and IL-2 production, and the levels of IL-2, IL-12 and IFN-γproduction in the serum,lymph nodes and spleen were also found to be higher in mice treated with AdMDC as compared with that in AdLacZ or PBS treated mice.The antitumor response of AdMDC was markedly impaired in IL-4 knockout mice,suggesting an essential role of IL-4 in the induction of antitumor immunity.These results suggest that MDC gene transfer elicited significant antitumor effects through enhancement of antitumor-immunity and might be of therapeutic potentials for immunotherapy of cancer.