A new development of FG-CC' siRNA blocking interaction of Tim-1 and Tim-4 can enhance DC vaccine against gastric cancer .
OBJECTIVE
Dendritic cells (DCs) are professional antigen-presenting cells responsible for initiating of immune response. However, because of immune tolerance, it is difficult to induce long-term tumor-specific immune response in humans. This is probably because DCs, which combine with Th2 in the Tim-1/Tim-4 pathway, will induce Th2 to proliferation.


METHODS
We have transfected siRNA of FG-CC' gene into DCs stimulated by gastric cancer lysate (lysate-FG-CC-siRNA group), FG-CC-siRNA will block FG-CC' loop,which plays an important role in interaction between Tim-1 and Tim-4. Their potential effect on gastric cancer immunotherapy is assessed by an experimental model.


RESULTS
It was observed that lysate-FG-CC-siRNA had the strongest ability of adjusting balance on the Thl/Th2, as a result, these DCs can inhibit gastric cancer growth. In order to test the ability of FG-CC-siR-NA DCs to inhibit tumor growth, we immunized mice subcutaneously with DCs transfected with FG-CC-siR-NA plus tumor antigen. Compared with the control group, a significant inhibition of tumor growth was obvious for the group of lysate-FG-CC-siRNA DC.


CONCLUSIONS
We have shown that FG-CC-siRNA blocks FG-CC'loop and significantly enhances the anti-tumor immunity in vitro and in vivo.
Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China. sunhuawenmail@gmail.com
Hua-Wen
HW
Sun
Chong
C
Wu
Hai-Yan
HY
Tan
Qiu-Shuang
QS
Wang
D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000235:genetics / Q000378:metabolism*; D019496:Cancer Vaccines; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D018274:Electroporation; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism*; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
D058846:Antibodies, Monoclonal, Murine-Derived; D019496:Cancer Vaccines; D016207:Cytokines; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D011991:Receptors, Virus; C512411:TIMD4 protein, human