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Spleen-derived dendritic cells engineered to enhance interleukin-12 production elicit therapeutic antitumor immune responses.

Both dendritic cells (DCs) and interleukin-12 (IL-12) can play immunostimulatory roles in vivo.

Therefore the use of a combination of these is a promising approach.

The authors used a murine tumor model to examine whether spleen-derived dendritic cells transduced with the Interleukin-12 gene could elicit tumor-specific immune responses. BALB/c mice injected peritumorally with adenovirus-mediated IL-12 gene-transduced antigen-unpulsed Dendritic cells inhibited the growth of day 5-established subcutaneous CT26 tumors.

Splenocytes from treated mice responded specifically to parental tumor cells and showed increased production of interferon gamma (IFN-gamma) and antitumor cytotoxic T-lymphocyte (CTL) activity.

Increased numbers of both CD4(+) and CD8(+) T cells were detected in the treated tumors.

The inhibition of tumor growth was significantly greater in mice injected with IL-12 gene-transduced DCs than in those injected with IL-12 gene-transduced fibroblasts or the IL-12 gene-encoding adenovirus itself.

Taken together, these results indicate that Dendritic cells transduced with the Interleukin-12 gene by a recombinant adenovirus are effective in inducing tumor-specific Th1 and CTL responses that inhibit the growth of established subcutaneous tumors.

Furumoto, K. et al. Int J Cancer 2000 Sep 1;87(5):665-72.





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