Enhanced immunotherapeutic effect of modified HPV16 E7-pulsed dendritic cell vaccine by an adeno-shRNA-SOCS1 virus

Abstract

Cervical cancer is the second most common cause of cancer-related deaths among women worldwide. However, no efficient therapy exists against cervical cancer and current treatments have several disadvantages. One possible novel approach is to develop immune-based strategies using tumor antigen-loaded dendritic cells (DCs) for the induction of cellular antitumor immunity. In this study, we created a modified HPV16 E7, HPV16mE7, to reduce its transformation activity and to enhance its antigenicity. The siRNA delivery technique was used to silence the suppressor of cytokine signaling 1 (SOCS1) gene in DCs. BM-derived DCs infected by ad-shRNA-SOCS1 were pulsed with the HPV16mE7 protein and then were transfused into mouse models bearing TC-1 tumor cells expressing HPV16 E6/E7. IFN-, cytokine (TNF-, IL-12, IL-6) expression, anti-E7 antibody and cytotoxic T lymphocyte (CTL) levels were measured. The survival rate, survival days and the tumor volume of the mouse models from the different treatment groups were monitored. The data showed that the mE7-pulsed DC vaccine enhanced by adenovirus-mediated SOCS1 silencing exhibited better immunotherapeutic effect on the allografted tumor mouse models. The method by silencing SOCS1 in HPV16mE7 protein-pulsed DCs may provide a new strategy for the development of safe and effective immunotherapy for cervical cancer.