한빛사 논문
Tae Jin Kim1,*, Hyun-Tak Jin2,*, Soo-Young Hur3, Hyun Gul Yang4, Yong Bok Seo4, Sung Ran Hong5, Chang-Woo Lee6, Suhyeon Kim6, Jung-Won Woo2, Ki Seok Park2, Youn-Young Hwang2, Jaehan Park2, In-Ho Lee1, Kyung-Taek Lim1, Ki-Heon Lee1, Mi Seon Jeong7, Charles D. Surh4,8, You Suk Suh2, Jong Sup Park3 & Young Chul Sung2,4
1 Department of Obstetrics and Gynecology, Cheil General Hospital and Women’s Healthcare Center, College of Medicine, Kwandong University, Seoul 100-380, Korea. 2 Research Institute, Genexine Inc., Korea Bio Park, Seongnam, Gyeonggi-do 463-400, Korea. 3 Department of Obstetrics and Gynecology, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea. 4 Division of Integrative Bioscience and Biotechnology, Pohang University of Science and Technology, Pohang 790-784, Korea. 5 Department of Pathology, Cheil General Hospital and Women’s Healthcare Center, College of Medicine, Kwandong University, Seoul 100-380, Korea. 6 Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi-do 440-746, Korea. 7 Laboratory of R&D for Genomics, Cheil General Hospital and Women’s Healthcare Center, College of Medicine, Kwandong University, Seoul 100-380, Korea. 8 Academy of Immunology and Microbiology, Institute of Basic Science, Pohang 790-784, Korea. * These authors contributed equally to this work.
Correspondence to: You Suk Suh or Young Chul Sung or Jong Sup Park
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.
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