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


CONCLUSIONS
Vaccination with recombinant AdVIL-12 transduced DC pulsed tumor cell lysate enhance anti-tumor immunity specific to colon cancer in mice.
He
Xiao-Zhou
XZ
Department of Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China.
Wang
Liang
L
Zhang
Yan-Yun
YY
D000230:Adenocarcinoma / Q000628:therapy*; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D019496:Cancer Vaccines / Q000235:genetics*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000628:therapy*; D003713:Dendritic Cells / Q000502:physiology / Q000637:transplantation*; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D016219:Immunotherapy, Adoptive / Q000379:methods; D018664:Interleukin-12 / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL
D019496:Cancer Vaccines; D018664:Interleukin-12