[Therapeutic effects of treatment of pancreatic carcinoma by interleukin-23 and apoptotic cell antigen-modified dendritic cell vaccine: experiment with mice].
OBJECTIVE
To investigate the therapeutic effects on pancreatic carcinoma by dendritic cells (DCs) transfected with interleukin (IL)-23 and acquiring apoptotic cell antigen.


METHODS
Murine IL-23 cDNA was subcloned into the vector so as to construct the eukaryotic dual-gene repression vector pcDNA3-IL-23. Bone-derived DCs were obtained from the long bones of extremities of normal C(57)BL/6 mice and were transfected with pcDNA3-IL-23. DCs cultured routinely and IL-23-transfected DCs were co-cultured with apoptotic tumor cells for 24 h so as to collect sensitized DCs acquiring the antigen of the apoptotic cells. Primary pancreatic carcinoma models were created in C(57)BL/6 mice with dimethyl-benzanthracene so as to obtain suspension of tumor cells. Thirty C(57)BL/6 mice were randomly divided into 5 groups: Group I (IL-23-transfected DC vaccine group, to be injected subcutaneously with IL-23 and apoptotic cells-modified DC vaccine twice with an interval of 7 d), Group II (apoptotic cells-sensitized DC vaccine group, to be injected subcutaneously with apoptotic cells-modified DC vaccine), Group III (IL-23 transfected DC group, to be injected with IL-23 transfected DCs), Group IV (un-modified DC group, to be injected with un-modified DCs), and Group V (control group, injected with normal saline). Seven days after the second injection suspension of tumor cells was injected subcutaneously, and then tumorigenesis was observed every other day. Another 30 C(57)BL/6 mice were divided into 5 groups as above-mentioned (Groups I - V(1)) and were killed 1 week after the inoculation of tumor cell suspension. Their spleens were taken out. The cytotoxic lymphocytes (CTLs) were isolated, co-cultured with IL-25 and apoptotic cells, and then tested for the secretion of interferon (IFN)-gamma and IL-4 by ELISA. Thirty C(57)BL/6 mice loading pancreatic carcinoma were randomly divided into 5 groups as above-mentioned (Groups I - V(2)) so as to observe the survival time.


RESULTS
ELISA showed that the IFN-gamma expression in the supernatant of culture fluid of IL-23 transfected DCs in Groups I(1) was significantly up-regulated (P < 0.01), and the IL-4 secretion of Group I(1) and Groups III(1) were both significantly lower than that of Group II(1) (both P < 0.05). The CTL civilities of Group I(1) and II(1) were both significantly higher than those of the other 3 groups (all P < 0.05). Four weeks after the inoculation tumorigenesis was not seen in Group I and was seen in Groups III and IV with an incidence of 33% - 50%. Tumorigenesis occurred only 1 week later in Group V. The tumor sizes of Groups I(2) and II(2) were both significantly smaller than those of the other 3 groups and the survival times of Groups I(2) and II(2) were both significantly lower than those of the other 3 groups (all P < 0.01).


CONCLUSIONS
IL-23 helps enhance the presenting ability of DC antigen. IL-23 modified vaccine strengthens the immune response of CTLs against specific tumor, thus inducing defensive immune response in the host and strengthening their active immune ability.
Tan
Guang
G
Department of General Surgery, First Affiliated Hospital, Dalian Medical University, Dalian 116011, China.
Wang
Zhong-Yu
ZY
Yin
Shuo
S
D000818:Animals; D017951:Antigen Presentation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005260:Female; D007167:Immunotherapy; D018664:Interleukin-12 / Q000235:genetics; D053759:Interleukin-23 / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000628:therapy*; D014162:Transfection
D053759:Interleukin-23; D018664:Interleukin-12