An effective vaccine against colon cancer in mice: Use of recombinant adenovirus interleukin-12 transduced dendritic cells.

摘要

AIM: To investigate the effect of a vaccine with recombinant adenovirus interleukin-12 (AdVIL-12) transduced dendritic cells (DCs) against colon cancer in mice. METHODS: DCs and AdVIL-12 were incubated together at different time intervals and at different doses. Supernatant was collected and tested for IL-12 by enzyme-linked immunosorbent assay (ELISA). In order to determine whether tumor cell lysate-pulsed (TP) AdVIL-12/DCs enhance therapeutic potential in the established tumor model, CT26 colon tumor cells were implanted subcutaneously (s.c.) in the midflank of naive BALB/c mice. Tumor-bearing mice were injected with a vaccination of CT26 TP AdVIL-12/DCs on d 3 and 10. As a protective colon tumor model, naive BALB/c mice were immunized s.c. in their abdomens with CT26 TP AdVIL-12/DCs twice at seven day intervals. After the immunization on d 7, the mice were challenged with a lethal dose of CT26 tumor cells and survival times were evaluated. Subsequently, cytotoxic T lymphocyte (CTL) activity and interferon gamma (IFNgamma) secretion was evaluated in the immunized mice, and assayed CTL ex vivo. RESULTS: Murine DCs were retrovirally transduced with AdVIL-12 efficiency, and the AdVIL-12 transduced DCs secreted a high level of IL-12 (AdVIL-12/DCs, 615.27 +/- 42.3 pg/mL vs DCs, 46.32 +/- 7.29 pg/mL, P < 0.05). Vaccination with CT26 TP AdVIL-12/DCs could enhance anti-tumor immunity against CT26 colon tumor in murine therapeutic models (tumor volume on d 19: CT26 TP AdVIL-12/DCs 107 +/- 42 mm(3) vs CT26 TP DCs 383 +/- 65 mm(3), P < 0.05) and protective models. Moreover, the CT26 TP AdVIL-12/DC vaccination enhances tumor-specific CTL activity, producing high levels of IFNgamma in immunized mice. Ex vivo primed T cells with AdVIL-12/DCs were able to induce more effective CTL activity than in primed T cells with CT26 TP/DCs (E:T = 100:1, 69.49% +/- 6.11% specific lysis vs 37.44% +/- 4.32% specific lysis, P < 0.05). CONCLUSION: Vaccination with recombinant AdVIL-12 transduced DC pulsed tumor cell lysate enhanceanti-tumor immunity specific to colon cancer in mice.