Clearance of persistent HPV infection and cervical lesion by therapeutic DNA vaccine in CIN3 patients

Tae Jin Kim, Hyun-Tak Jin, Soo-Young Hur, Hyun Gul Yang, Yong Bok Seo, Sung Ran Hong, Chang-Woo Lee, Suhyeon Kim, Jung-Won Woo, Ki Seok Park, Youn-Young Hwang, Jaehan Park, In-Ho Lee, Kyung-Taek Lim, Ki-Heon Lee, Mi Seon Jeong, Charles D. Surh, You Suk Suh (), Jong Sup Park () and Young Chul Sung ()
Additional contact information
Tae Jin Kim: Cheil General Hospital and Women’s Healthcare Center, College of Medicine, Kwandong University
Hyun-Tak Jin: Research Institute, Genexine Inc., Korea Bio Park
Soo-Young Hur: Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea
Hyun Gul Yang: Pohang University of Science and Technology
Yong Bok Seo: Pohang University of Science and Technology
Sung Ran Hong: Cheil General Hospital and Women’s Healthcare Center, College of Medicine, Kwandong University
Chang-Woo Lee: Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine
Suhyeon Kim: Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine
Jung-Won Woo: Research Institute, Genexine Inc., Korea Bio Park
Ki Seok Park: Research Institute, Genexine Inc., Korea Bio Park
Youn-Young Hwang: Research Institute, Genexine Inc., Korea Bio Park
Jaehan Park: Research Institute, Genexine Inc., Korea Bio Park
In-Ho Lee: Cheil General Hospital and Women’s Healthcare Center, College of Medicine, Kwandong University
Kyung-Taek Lim: Cheil General Hospital and Women’s Healthcare Center, College of Medicine, Kwandong University
Ki-Heon Lee: Cheil General Hospital and Women’s Healthcare Center, College of Medicine, Kwandong University
Mi Seon Jeong: Laboratory of R&D for Genomics, Cheil General Hospital and Women’s Healthcare Center, College of Medicine, Kwandong University
Charles D. Surh: Pohang University of Science and Technology
You Suk Suh: Research Institute, Genexine Inc., Korea Bio Park
Jong Sup Park: Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea
Young Chul Sung: Research Institute, Genexine Inc., Korea Bio Park

Nature Communications, 2014, vol. 5, issue 1, 1-14

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms6317

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