title: Intravaginal Administration of Fc-Fused IL7 Suppresses the Cervicovaginal Tumor by Recruiting HPV DNA Vaccine-Induced CD8 T Cells.
abstract: OBJECTIVE
  The induction of tissue-localized virus-specific CD8 T-cell response is essential for the development of an effective therapeutic vaccine against genital diseases, such as cervical cancer and genital herpes. Here, we aimed to elucidate the immunologic role of IL7 in the induction of mucosal cellular immunity.
  
  
  METHODS
  IL7 was engineered through Fc fusion to enhance mucosal delivery across the genital epithelial barrier. The immunomodulatory role of IL7 was evaluated by monitoring the kinetics of various immune cells and measuring the expression of chemokines and cytokines after intravaginal administration of Fc-fused IL7 (IL7-Fc). The antitumor effects of intramuscular human papillomavirus (HPV) DNA vaccine or topical IL7-Fc alone or in a combinational regimen on mice survival were compared using a orthotopic cervical cancer model.
  
  
  RESULTS
  Intravaginal treatment of IL7-Fc, but not native IL7, induces upregulation of chemokines (CXCL10, CCL3, CCL4, and CCL5), cytokines (IFNγ, TNFα, IL6, and IL1β), and an adhesion molecule (VCAM-1) in the genital tract, leading to the recruitment of several leukocytes, including CD4, CD8, γδ T cells, and dendritic cells. Importantly, in this murine cervical cancer model, topical administration of IL7-Fc after intramuscular HPV DNA vaccination increases the number of HPV-specific CD8 T cells in the genital mucosa, but not in the spleen, leading to stronger antitumor activity than the HPV DNA vaccine alone.
  
  
  CONCLUSIONS
  Our findings provide an important insight into the immunomodulatory role of IL7-Fc via topical application and the design of therapeutic vaccine regimen that induces effective genital-mucosal CD8 T-cell responses. Clin Cancer Res; 22(23); 5898-908. ©2016 AACR.
authors.affiliation: Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, Republic of Korea.
authors.forename: Young Woo
authors.initials: YW
authors.lastname: Choi
authors.affiliation: Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, Republic of Korea.
authors.forename: Moon Cheol
authors.initials: MC
authors.lastname: Kang
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, Republic of Korea.
authors.forename: Yong Bok
authors.initials: YB
authors.lastname: Seo
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, Republic of Korea.
authors.forename: Hong
authors.initials: H
authors.lastname: Namkoong
authors.affiliation: Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, Republic of Korea.
authors.forename: Yunji
authors.initials: Y
authors.lastname: Park
authors.affiliation: Research Institute, Genexine Inc., Korea Bio Park, Seongnam, Gyeonggi-do, Republic of Korea.
authors.forename: Dong-Hoon
authors.initials: DH
authors.lastname: Choi
authors.affiliation: Research Institute, Genexine Inc., Korea Bio Park, Seongnam, Gyeonggi-do, Republic of Korea.
authors.forename: You Suk
authors.initials: YS
authors.lastname: Suh
authors.affiliation: Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, Republic of Korea.|Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, Republic of Korea.
authors.forename: Seung-Woo
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, Republic of Korea. ycsung@postech.ac.kr htjin@biodion.com.|Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, Republic of Korea.|Research Institute, Genexine Inc., Korea Bio Park, Seongnam, Gyeonggi-do, Republic of Korea.
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Sung
authors.affiliation: Research Institute, Biodion Inc, Korea Bio Park, Seongnam, Gyeonggi-do, Republic of Korea. ycsung@postech.ac.kr htjin@biodion.com.
authors.forename: Hyun-Tak
authors.initials: HT
authors.lastname: Jin
mesh_terms: D000282:Administration, Intravaginal; D052685:Alphapapillomavirus / Q000276:immunology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D007111:Immunity, Cellular / Q000276:immunology; D015851:Interleukin-7 / Q000008:administration & dosage* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D030361:Papillomavirus Infections / Q000276:immunology; D053918:Papillomavirus Vaccines / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000821:virology; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D016207:Cytokines; D015851:Interleukin-7; D053918:Papillomavirus Vaccines; D019444:Vaccines, DNA