title: Clearance of persistent HPV infection and cervical lesion by therapeutic DNA vaccine in CIN3 patients.
abstract: Here, we demonstrate that electroporation-enhanced immunization with a rationally designed HPV DNA vaccine (GX-188E), preferentially targeting HPV antigens to dendritic cells, elicits a significant E6/E7-specific IFN-γ-producing T-cell response in all nine cervical intraepithelial neoplasia 3 (CIN3) patients. Importantly, eight out of nine patients exhibit an enhanced polyfunctional HPV-specific CD8 T-cell response as shown by an increase in cytolytic activity, proliferative capacity and secretion of effector molecules. Notably, seven out of nine patients display complete regression of their lesions and viral clearance within 36 weeks of follow up. GX-188E administration does not elicit serious vaccine-associated adverse events at all administered doses. These findings indicate that the magnitude of systemic polyfunctional CD8 T-cell response is the main contributing factor for histological, cytological and virological responses, providing valuable insights into the design of therapeutic vaccines for effectively treating persistent infections and cancers in humans.
authors.affiliation: Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, College of Medicine, Kwandong University, Seoul 100-380, Korea.
authors.forename: Tae Jin
authors.initials: TJ
authors.lastname: Kim
authors.affiliation: Research Institute, Genexine Inc., Korea Bio Park, Seongnam, Gyeonggi-do 463-400, Korea.
authors.forename: Hyun-Tak
authors.initials: HT
authors.lastname: Jin
authors.affiliation: Department of Obstetrics and Gynecology, Seoul St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea.
authors.forename: Soo-Young
authors.initials: SY
authors.lastname: Hur
authors.affiliation: Division of Integrative Bioscience and Biotechnology, Pohang University of Science and Technology, Pohang 790-784, Korea.
authors.forename: Hyun Gul
authors.initials: HG
authors.lastname: Yang
authors.affiliation: Division of Integrative Bioscience and Biotechnology, Pohang University of Science and Technology, Pohang 790-784, Korea.
authors.forename: Yong Bok
authors.initials: YB
authors.lastname: Seo
authors.affiliation: Department of Pathology, Cheil General Hospital and Women's Healthcare Center, College of Medicine, Kwandong University, Seoul 100-380, Korea.
authors.forename: Sung Ran
authors.initials: SR
authors.lastname: Hong
authors.affiliation: Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi-do 440-746, Korea.
authors.forename: Chang-Woo
authors.initials: CW
authors.lastname: Lee
authors.affiliation: Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi-do 440-746, Korea.
authors.forename: Suhyeon
authors.initials: S
authors.lastname: Kim
authors.affiliation: Research Institute, Genexine Inc., Korea Bio Park, Seongnam, Gyeonggi-do 463-400, Korea.
authors.forename: Jung-Won
authors.initials: JW
authors.lastname: Woo
authors.affiliation: Research Institute, Genexine Inc., Korea Bio Park, Seongnam, Gyeonggi-do 463-400, Korea.
authors.forename: Ki Seok
authors.initials: KS
authors.lastname: Park
authors.affiliation: Research Institute, Genexine Inc., Korea Bio Park, Seongnam, Gyeonggi-do 463-400, Korea.
authors.forename: Youn-Young
authors.initials: YY
authors.lastname: Hwang
authors.affiliation: Research Institute, Genexine Inc., Korea Bio Park, Seongnam, Gyeonggi-do 463-400, Korea.
authors.forename: Jaehan
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, College of Medicine, Kwandong University, Seoul 100-380, Korea.
authors.forename: In-Ho
authors.initials: IH
authors.lastname: Lee
authors.affiliation: Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, College of Medicine, Kwandong University, Seoul 100-380, Korea.
authors.forename: Kyung-Taek
authors.initials: KT
authors.lastname: Lim
authors.affiliation: Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, College of Medicine, Kwandong University, Seoul 100-380, Korea.
authors.forename: Ki-Heon
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Laboratory of R&D for Genomics, Cheil General Hospital and Women's Healthcare Center, College of Medicine, Kwandong University, Seoul 100-380, Korea.
authors.forename: Mi Seon
authors.initials: MS
authors.lastname: Jeong
authors.affiliation: 1] Division of Integrative Bioscience and Biotechnology, Pohang University of Science and Technology, Pohang 790-784, Korea [2] Academy of Immunology and Microbiology, Institute of Basic Science, Pohang 790-784, Korea.
authors.forename: Charles D
authors.initials: CD
authors.lastname: Surh
authors.affiliation: Research Institute, Genexine Inc., Korea Bio Park, Seongnam, Gyeonggi-do 463-400, Korea.
authors.forename: You Suk
authors.initials: YS
authors.lastname: Suh
authors.affiliation: Department of Obstetrics and Gynecology, Seoul St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea.
authors.forename: Jong Sup
authors.initials: JS
authors.lastname: Park
authors.affiliation: 1] Research Institute, Genexine Inc., Korea Bio Park, Seongnam, Gyeonggi-do 463-400, Korea [2] Division of Integrative Bioscience and Biotechnology, Pohang University of Science and Technology, Pohang 790-784, Korea.
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Sung
mesh_terms: D000328:Adult; D000917:Antibody Formation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000276:immunology; D030361:Papillomavirus Infections / Q000628:therapy*; D053918:Papillomavirus Vaccines / Q000627:therapeutic use*; D002583:Uterine Cervical Neoplasms / Q000628:therapy* / Q000821:virology; D019444:Vaccines, DNA / Q000627:therapeutic use*; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000628:therapy* / Q000821:virology
chemical_list: C000604106:GX-188 vaccine; D009856:Oncogene Proteins, Viral; D053918:Papillomavirus Vaccines; D019444:Vaccines, DNA