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

The major goal in cancer immunotherapy is the induction of tumor‐specific T lymphocytes capable of killing tumor cells. As both dendritic cells (DCs) and interleukin‐12 (IL‐12) can play immunostimulatory roles in vivo, the use of a combination of these has become a promising approach. In the present study, we used a murine tumor model to examine whether spleen‐derived DCs transduced with the IL‐12 gene could elicit tumor‐specific immune responses. BALB/c mice injected peritumorally with adenovirus‐mediated IL‐12 gene‐transduced antigen‐unpulsed DCs 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‐γ) 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 DCs transduced with the IL‐12 gene by a recombinant adenovirus are effective in inducing tumor‐specific Th1 and CTL responses that inhibit the growth of established subcutaneous tumors. Int. J. Cancer 87:665–672, 2000. © 2000 Wiley‐Liss, Inc.