title: Fusion of CTLA-4 with HPV16 E7 and E6 enhanced the potency of therapeutic HPV DNA vaccine.
abstract: Preventive anti-HPV vaccines are effective against HPV infection but not against existing HPV-associated diseases, including cervical cancer and other malignant diseases. Therefore, the development of therapeutic vaccines is urgently needed. To improve anti-tumor effects of therapeutic vaccine, we fused cytotoxic T-lymphocyte antigen 4 (CTLA-4) with HPV16 E7 and E6 as a fusion therapeutic DNA vaccine (pCTLA4-E7E6). pCTLA4-E7E6 induced significantly higher anti-E7E6 specific antibodies and relatively stronger specific CTL responses than the nonfusion DNA vaccine pE7E6 in C57BL/6 mice bearing with TC-1 tumors. pCTLA4-E7E6 showed relatively stronger anti-tumor effects than pE7E6 in therapeutic immunization. These results suggest that fusing CTLA-4 with E7E6 is a useful strategy to develop therapeutic HPV DNA vaccines. In addition, fusing the C-terminal of E7 with the N-terminal of E6 impaired the functions of both E7 and E6.
authors.affiliation: Hubei-MOST KLOS & KLOBME, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, PR China.
authors.forename: Lili
authors.initials: L
authors.lastname: Gan
authors.affiliation: Hubei-MOST KLOS & KLOBME, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, PR China.
authors.forename: Rong
authors.initials: R
authors.lastname: Jia
authors.affiliation: Hubei-MOST KLOS & KLOBME, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, PR China.
authors.forename: Lili
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Hubei-MOST KLOS & KLOBME, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, PR China; Department of Endodontics, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, PR China.
authors.forename: Jihua
authors.initials: J
authors.lastname: Guo
authors.affiliation: Hubei-MOST KLOS & KLOBME, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei, PR China.
authors.forename: Mingwen
authors.initials: M
authors.lastname: Fan
mesh_terms: D000818:Animals; D015153:Blotting, Western; D060908:CTLA-4 Antigen / Q000276:immunology*; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D006801:Humans; D008810:Mice, Inbred C57BL; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D050725:Papillomavirus E7 Proteins / Q000276:immunology*; D053918:Papillomavirus Vaccines / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D012097:Repressor Proteins / Q000276:immunology*; D016160:Retinoblastoma Protein / Q000378:metabolism; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D060908:CTLA-4 Antigen; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D019444:Vaccines, DNA; C059731:oncogene protein E7, Human papillomavirus type 16