title: In vitro and ex vivo evaluation of a multi-epitope heparinase vaccine for various malignancies.
abstract: Previous studies have indicated that heparanase (Hpa) might represent a candidate universal tumor-associated antigen. However, vaccine therapy targeting only one cytotoxic T lymphocyte (CTL) epitope is suboptimal in preventing cancer. In the present study, we designed heparanase multi-epitope vaccines to increase the immune response to standard single heparanase epitopes. The results showed that multi-epitope vaccines Hpa525 + 277 + 405 + 16 and Hpa8 + 310 + 315 + 363 induced higher Hpa-specific lysis of various cancer cells from different tissues in a HLA-A2-restricted and heparanase-specific manner compared with the single epitope vaccines Hpa525, Hpa277, Hpa405, Hpa16, Hpa8, Hpa310, Hpa315 and Hpa363, both in vitro and ex vivo. Heparanase multi-epitope vaccines not only induced the heparanase-specific CTL to lyse tumor cells but also increased CTL secretion of interferon-γ. However, these heparanase-specific CTL did not lyse heparanase-expressing autologous lymphocytes and dendritic cells, which confirms the safety of these multi-epitope vaccines. Therefore, the present study provides theoretical evidence for the use of heparanase multi-epitope vaccines for clinical application.
authors.affiliation: Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China; Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Xu-Dong
authors.initials: XD
authors.lastname: Tang
authors.forename: Shu-Liang
authors.initials: SL
authors.lastname: Guo
authors.forename: Guo-Zhen
authors.initials: GZ
authors.lastname: Wang
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Yu-Yun
authors.initials: YY
authors.lastname: Wu
authors.forename: Dian-Chun
authors.initials: DC
authors.lastname: Fang
authors.forename: Ya-Han
authors.initials: YH
authors.lastname: Fan
authors.forename: Shi-Ming
authors.initials: SM
authors.lastname: Yang
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D000939:Epitopes / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology; D056945:Hep G2 Cells; D019763:Heparin Lyase / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D061986:MCF-7 Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D000939:Epitopes; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D007371:Interferon-gamma; D019763:Heparin Lyase
keywords: Dendritic cells; epitopes; heparanase; immunotherapy; tumor antigens