Spleen-derived dendritic cells engineered to enhance interleukin-12 production elicit therapeutic antitumor immune responses
✍ Scribed by Katsuyoshi Furumoto; Shigeki Arii; Seiji Yamasaki; Masaki Mizumoto; Akira Mori; Naoya Inoue; Naoki Isobe; Masayuki Imamura
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- French
- Weight
- 461 KB
- Volume
- 87
- Category
- Article
- ISSN
- 0020-7136
No coin nor oath required. For personal study only.
✦ Synopsis
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 genetransduced 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-␥) 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 genetransduced 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.