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IL-12遺伝子導入樹状細胞 (dendritic cells) の腫瘍内投与を用いた癌免疫療法：西岡安彦^１,２, 田原秀晃^１（ピッツバーグ大・外科^１, 徳島大・医・三内^２）

Antitumor effects of intratumoral injection with IL-12 gene-modified dendritic cells (DC's): Yasuhiko NISHIOKA^1,2, Hideaki TAHARA¹ (¹ Dept. of Surgery, Univ. of Pittsburgh, USA, ² Third Dept. of Int. Med., Univ. of Tokushima)

Effective antitumor immune response might be induced with the delivery of activated DC's to the site of tumor antigen. However, DC functions could be disturbed within the tumor microenvironment. In this study, we investigated the antitumor effects of intratumoral injection of murine bone marrow (BM) - derived DC's retrovirally transduced with the gene encoding IL-12. Centrifugal retroviral transduction was performed 3 times on day 2, 3 and 4 for BM cells cultured with GM-CSF and IL-4. A study using marker genes (hCD80 and EGFP) confirmed that BM-DC's could be transduced at high efficiency (20 - 75%) using retroviral supernatant. BM-DC's transduced with the genes encoding mIL-12 stably expressed bioactive IL-12 protein at high levels (4 - 80 ng/10⁶ cells/48 h). FACS analysis showed that IL-12 transduced DCs have an increased level of class II expression, but similar levels of CD56, CD80 and CD86 when compared with those of control DCs. Intratumoral injection with IL-12 gene-modified BM-DC's resulted in regression of all day 7 established, poorly or non-immunogenic tumors (MCA205, MCA207, B16 and D122). This antitumor effects was substantially better than IL-12-transduced syngeneic fibroblasts. Furthermore intratumoral injection with IL-12-transduced DC's induced specific Th1 responses to tumor in regional lymph nodes and spleen at levels much greater than that of IL-12-transduced fibroblasts, and un-injected contralateral tumors showed significant regression. These results indicate that this strategy is very effective in inducing systemic antitumor immunity, and support its clinical application for patients with various types of cancer.