title: Enhanced anti-tumor effects of HPV16E7(49-57)-based vaccine by combined immunization with poly(I:C) and oxygen-regulated protein 150.
abstract: BACKGROUND
  It is well known that both heat shock protein (HSP) and Toll-like receptor (TLR)3 agonist polyinosinic:polycytidylic acid (poly(I:C)) are capable of promoting the antigen-specific immune responses. In the current study, we assessed whether the anti-tumor effects of the HPV16E7(49-57)-based vaccine can be elevated by combined applications of poly(I:C) and oxygen-regulated protein 150 (ORP150) in a mouse cervical cancer model.
  
  
  METHODS
  Recombinant mouse ORP150 and HPV E7(49-57) peptide were combined to passively form the ORP150-E7(49-57) complex under heat shock conditions. The effects of ORP150-E7(49-57) complex plus poly(I:C) adjuvant on lymphocyte proliferation and functional cytotoxic T cells were investigated by methyl thiazolyl tetrazolium (MTT), ELISPOT, and non-radioactive cytotoxicity assays. Finally, the complex's therapeutic anti-tumor effects with and without adjuvant therapy were observed in a tumor challenge experiment.
  
  
  RESULTS
  This combination vaccine approach significantly enhanced the proliferation of splenocytes and induced strong E7(49-57)-specific CTL responses. More importantly, the ORP150-E7(49-57) complex plus poly(I:C) vaccine format demonstrated more potent anti-tumor effects than ORP150-E7(49-57) complex alone or E7(49-57) plus poly(I:C) in TC-1 tumor-bearing mice.
  
  
  CONCLUSIONS
  Both poly(I:C) and ORP150 chaperone can synergistically enhance the anti-tumor effects of the HPV16E7(49-57)-based vaccine in vitro and in vivo. This strategy provides a platform for the design of a tumor therapeutic vaccine capable of inducing an effective anti-tumor immune response.
authors.affiliation: Department of Dermatovenereology, First Affiliated Hospital, Institute of Dermatovenereology, Wenzhou Medical College, Wenzhou 325000, China.
authors.forename: Shisheng
authors.initials: S
authors.lastname: Chen
authors.forename: Rongying
authors.initials: R
authors.lastname: Ou
authors.forename: Jun
authors.initials: J
authors.lastname: Tang
authors.forename: Xiufang
authors.initials: X
authors.lastname: Deng
authors.forename: Yuzhang
authors.initials: Y
authors.lastname: Wu
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: van Velkinburgh
authors.forename: Bing
authors.initials: B
authors.lastname: Ni
authors.forename: Yunsheng
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005260:Female; D018840:HSP70 Heat-Shock Proteins; D052162:Human papillomavirus 16 / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D050725:Papillomavirus E7 Proteins / Q000276:immunology*; D030361:Papillomavirus Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D010446:Peptide Fragments / Q000276:immunology; D011070:Poly I-C / Q000008:administration & dosage*; D011506:Proteins / Q000008:administration & dosage*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D014611:Vaccination; D017778:Vaccines, Combined; D023041:Xenograft Model Antitumor Assays
chemical_list: D019496:Cancer Vaccines; D018840:HSP70 Heat-Shock Proteins; D050725:Papillomavirus E7 Proteins; D010446:Peptide Fragments; D011506:Proteins; D017778:Vaccines, Combined; C059731:oncogene protein E7, Human papillomavirus type 16; C050087:oxygen-regulated proteins; D011070:Poly I-C