title: Antitumor therapeutic and antimetastatic activity of electroporation-delivered human papillomavirus 16 E7 DNA vaccines: a possible mechanism for enhanced tumor control.
abstract: DNA vaccines are known to be lacking in immunogenicity in humans. Presently, electroporation (EP) is thought to overcome this limitation. Here, we investigate whether human papillomavirus 16 E7 DNA vaccines delivered by EP might elicit potent antitumor activity in animal cervical cancer models, with a focus on the underlying mechanism(s). Intramuscular (IM)-EP delivery of E7 DNA vaccines induced more potent antitumor therapeutic and antimetastatic activity compared with IM delivery. Moreover, the tumor-controlled animals by IM-EP possessed long-term memory responses to parental tumor cells. This improved antitumor effect was concomitant with augmented Ag-specific CTL activities. IM-EP also induced IgG and Th-cell responses higher than IM delivery. Finally, IM-EP resulted in more antigen production in and more attraction of immune cells into the site of DNA injection, suggesting that these biological and immunological changes made by IM-EP might be responsible for enhanced CTL activities and antitumor resistance. Thus, this study shows that IM-EP can induce more potent antitumor activity by augmenting CTL responses possibly through more antigen production in and more attraction of immune cells into the muscle sites. This study also suggests that IM-EP of E7 DNA vaccines might be a potential approach toward treating patients with cervical cancer.
authors.affiliation: Department of Internal Medicine, Catholic University of Daegu, Daegu, Korea.
authors.forename: In Hee
authors.initials: IH
authors.lastname: Lee
authors.forename: Jae-Bok
authors.initials: JB
authors.lastname: Park
authors.forename: Minseon
authors.initials: M
authors.lastname: Cheong
authors.forename: Youn Seok
authors.initials: YS
authors.lastname: Choi
authors.forename: Daehan
authors.initials: D
authors.lastname: Park
authors.forename: Jeong-Im
authors.initials: JI
authors.lastname: Sin
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D002461:Cell Line, Transformed / Q000637:transplantation / Q000821:virology; D004195:Disease Models, Animal; D004354:Drug Screening Assays, Antitumor; D018274:Electroporation; D004847:Epithelial Cells / Q000637:transplantation / Q000821:virology; D005260:Female; D052162:Human papillomavirus 16 / Q000276:immunology*; D006801:Humans; D007115:Immunization Schedule; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000032:analysis; D008168:Lung / Q000166:cytology; D008175:Lung Neoplasms / Q000556:secondary / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology / Q000556:secondary / Q000628:therapy; D050725:Papillomavirus E7 Proteins / Q000276:immunology*; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D040521:Subcutaneous Tissue; D002583:Uterine Cervical Neoplasms; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D019496:Cancer Vaccines; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D019444:Vaccines, DNA; C059731:oncogene protein E7, Human papillomavirus type 16; D007371:Interferon-gamma