The immunotherapeutic effect of dendritic cells vaccine modified with interleukin-18 gene and tumor cell lysate on mice with pancreatic carcinoma.
OBJECTIVE
To estimate the effect of a therapeutic vaccine against pancreatic carcinoma based on dendritic cell (DC) vaccine modified with tumor lysate and Interleukin-18 gene.


METHODS
The BALB/C mice model of pancreatic carcinoma was induced with DMBA. DC vaccine was constructed through pulsed with tumor lysate and transfected by the recombinant adenoviral vector encoding IL-18 gene. The immunotherapeutic effects of DC vaccine on mice with pancreatic carcinoma were assessed (divided into DC-IL18-Lysate group, DC-Lysate group, DC-IL18 group, DC group, PBS group).


RESULTS
After vaccination of the DC vaccine, the concentration of IL-18 and IFN-gamma were 2161+/-439 ng x L(-1) and 435+/-72 ng x L(-1) in DC-IL18-Lysate group and there was significant difference compared with other groups (P<0.01). After vaccination of the DC vaccine, the transplanted tumors were observed on 30 days in DC-Lysate groups, on 16 days in DC-IL18 groups, on 3 days in control group, but mice remained tumor-free for at least 50 days in DC-IL18-Lysate group and there was significant difference between DC-IL18-Lysate group and other groups (P<0.01). The median survival exceeds 62 days in DC-IL18-Lysate group. But the median survival was 48.6 days in DC-Lysate group, 33 days in DC-IL18 group, 17 days in PBS group. The survival period was obviously prolonged in DC-IL18-Lysate group than in other groups (P<0.05, P<0.01). The weight of pancreatic tumor was 0.22+/-0.083 g in DC-IL18-Lysate group, 1.45+/-0.74 g in DC-Lysate group, 1.89+/-1.34 g in DC-IL18 group, 3.0+/-1.6 g in DC group, 2.9+/-2.0 g in PBS group and the weight of tumor obviously reduced in DC-IL18-Lysate group than in other groups (P<0.05, P<0.01).


CONCLUSIONS
DC vaccine modified with tumor lysate and Interleukin-18 gene can induce a specific and effective immune response against pancreatic carcinoma cell.
Tang
Zhao-Hui
ZH
Department of General Surgery of Tong Ji Hospital, Wuhan 430030, Hubei Province, China. tangzh45@sina.com
Qiu
Wen-Hong
WH
Wu
Gao-Song
GS
Yang
Xiang-Ping
XP
Zou
Sheng-Quan
SQ
Qiu
Fa-Zu
FZ
D000818:Animals; D019496:Cancer Vaccines / Q000235:genetics* / Q000494:pharmacology*; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D007167:Immunotherapy; D007371:Interferon-gamma / Q000097:blood; D020382:Interleukin-18 / Q000097:blood / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000628:therapy*; D013154:Spleen / Q000166:cytology; D014407:Tumor Cells, Cultured
D019496:Cancer Vaccines; D020382:Interleukin-18; D007371:Interferon-gamma