title: 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-γ, cytokine (TNF-α, 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.
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, P.R. China.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Zhu
authors.forename: Yi
authors.initials: Y
authors.lastname: Zheng
authors.forename: Lin
authors.initials: L
authors.lastname: Mei
authors.forename: Mengqiong
authors.initials: M
authors.lastname: Liu
authors.forename: Shanshan
authors.initials: S
authors.lastname: Li
authors.forename: Huawei
authors.initials: H
authors.lastname: Xiao
authors.forename: Huijun
authors.initials: H
authors.lastname: Zhu
authors.forename: Shu
authors.initials: S
authors.lastname: Wu
authors.forename: Hongbo
authors.initials: H
authors.lastname: Chen
authors.forename: Laiqiang
authors.initials: L
authors.lastname: Huang
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000951:Antigens, Neoplasm / Q000008:administration & dosage / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007167:Immunotherapy; D051379:Mice; D050725:Papillomavirus E7 Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D034741:RNA, Small Interfering; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D050725:Papillomavirus E7 Proteins; D034741:RNA, Small Interfering; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C059731:oncogene protein E7, Human papillomavirus type 16