title: Heat shock protein 110 improves the antitumor effects of the cytotoxic T lymphocyte epitope E7(49-57) in mice.
abstract: Several strategies have been used to enhance the vaccine-induced immunity of peptide vaccines and effective therapeutic benefits, including the utilization of heat shock proteins (HSP), especially the HSP70 family. HSP110 exhibits a higher binding affinity with protein and is capable of enhancing the immunogenicity of protein antigens; however, whether HSP110 can also increase the efficiency of peptide vaccine remains unclear. Here, we investigated mHSP110 as a chaperone immunoadjuvant to enhance the immune response to HPV16 oncoprotein E7-derived CTL epitope E7(49-57) in a mouse model. We developed the HSP110-E7(49-57) complex and demonstrated that mHSP110 could form complexes with peptide E7(49-57) using FITC-labeled E7(49-57) as the tracer. Inoculation of the mHSP110-E7(49-57) complex was capable of priming strong epitope-specific immune response as determined by its ability to elicit an epitope-specific splenocytes proliferation and a cytotoxic T cell response, and IFNgamma production in splenocytes. Results also showed that immunization with the mHSP110-E7(49-57) complex completely protected mice against subsequent challenge with tumor cells. More importantly, immunization of this complex also significantly inhibited the growth of established tumors and prolonged the survival time of the tumor-bearing animals. Thus, mHSP110-E7(49-57) complex vaccine represents a potentially powerful approach for use in the immunotherapy of cervical cancer associated with HPV16 infection. More importantly, the multi-epitopes derived from E7 and other E proteins can be applied to the strategy described in this study to form a multi-antigenic vaccine to induce an improved antitumor immune response to cervical cancer in the future.
authors.affiliation: Department of dermatovenereology, First Affiliated Hospital, Institute of Dermatovenereology, Wenzhou Medical College, Wenzhou, China.
authors.forename: Faliang
authors.initials: F
authors.lastname: Ren
authors.forename: Yunsheng
authors.initials: Y
authors.lastname: Xu
authors.forename: Liwei
authors.initials: L
authors.lastname: Mao
authors.forename: Rongying
authors.initials: R
authors.lastname: Ou
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Ding
authors.forename: Xueqi
authors.initials: X
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Tang
authors.forename: Bingxu
authors.initials: B
authors.lastname: Li
authors.forename: Zhengcai
authors.initials: Z
authors.lastname: Jia
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Tian
authors.forename: Bing
authors.initials: B
authors.lastname: Ni
authors.forename: Yuzhang
authors.initials: Y
authors.lastname: Wu
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry; D000818:Animals; D000956:Antigens, Viral / Q000737:chemistry / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor / Q000637:transplantation; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D005260:Female; D050957:HSP110 Heat-Shock Proteins / Q000737:chemistry / Q000276:immunology*; D052162:Human papillomavirus 16 / Q000276:immunology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D050725:Papillomavirus E7 Proteins / Q000737:chemistry / Q000276:immunology*; D030361:Papillomavirus Infections / Q000276:immunology / Q000517:prevention & control*; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000821:virology; D014611:Vaccination; D014765:Viral Vaccines / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000276:Adjuvants, Immunologic; D000956:Antigens, Viral; D019496:Cancer Vaccines; D000939:Epitopes; D050957:HSP110 Heat-Shock Proteins; D050725:Papillomavirus E7 Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D014765:Viral Vaccines; C059731:oncogene protein E7, Human papillomavirus type 16