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 nave 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,nave 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 (IFNγ) secretion was evaluated in the immunized mice,and assayed CTL ex vivo. RESULTS: Murine DCs were retrovirally transduced with AdVIL-12 effi ciency,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 mm3 vs CT26 TP DCs 383 ± 65 mm3,P < 0.05) and protective models. Moreover,the CT26 TP AdVIL-12/DC vaccination enhances tumor-specific CTL activity,producing high levels of IFNγ 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% specif ic lysis vs 37.44% ± 4.32% specifi c lysis,P < 0.05). CONCLUSION: Vaccination with recombinant AdVIL-12 transduced DC pulsed tumor cell lysate enhance anti-tumor immunity specifi c to colon cancer in mice.