Colorectal Cancer
Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Jan 28, 2008; 14(4): 532-540
Published online Jan 28, 2008. doi: 10.3748/wjg.14.532
An effective vaccine against colon cancer in mice: Use of recombinant adenovirus interleukin-12 transduced dendritic cells
Xiao-Zhou He, Liang Wang, Yan-Yun Zhang
Xiao-Zhou He, Department of Surgery, The First People Hospital of Changzhou, Changzhou 213000, Jiangsu Province, China
Liang Wang, Department of Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
Yan-Yun Zhang, Health Science Center of Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China
Correspondence to: Dr. Liang Wang, Department of Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China.
Telephone: +86-519-86180003
Fax: +86-519-86621235
Received: July 20, 2007
Revised: September 1, 2007
Published online: January 28, 2008

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 naïve 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, naïve 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 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 mm3vs 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% 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 anti-tumor immunity specific to colon cancer in mice.

Keywords: Vaccination, Dendritic cells, Cytokine, Interleukin-12, Colon cancer, Immunotherapy