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

• Published in: World journal of gastroenterology : WJG Vol. 14; no. 4; pp. 532 - 540
• Main Authors: He, Xiao-Zhou, Wang, Liang, Zhang, Yan-Yun
• Format: Journal Article
• Language: English
• Published: United States Department of Surgery, the First People Hospital of Changzhou, Changzhou 213000, Jiangsu Province, China%Department of Surgery, the First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China%Health Science Center of Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China 28.01.2008; The WJG Press and Baishideng
• Subjects: Adenocarcinoma - therapy; Adenoviridae - genetics; Animals; Cancer Vaccines - genetics; Cell Line, Tumor; Colonic Neoplasms - therapy; Colorectal Cancer; Dendritic Cells - physiology; Dendritic Cells - transplantation; Female; Genetic Therapy - methods; Immunotherapy, Adoptive - methods; Interleukin-12 - genetics; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; 树突细胞; 疫苗接种; 白细胞介素-12; 细胞因子; 结肠癌; Colon cancer; Dendritic cells; Vaccination; Interleukin-12; Immunotherapy; Cytokine
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.14.532

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 （IFNy） 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 IFN7 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 enhance antitumor immunity specific to colon cancer in mice.