title: Cytotoxic T lymphocyte epitopes from human heparanase can elicit a potent anti-tumor immune response in mice.
abstract: Heparanase is expressed in almost all advanced tumors, and therefore it may serve as a potential target for tumor therapy. Our previous study has shown that heparanase can serve as a potential universal tumor-associated antigen (TAA) for the immunotherapy of advanced tumors. Further study demonstrated that the HLA-A*0201-restricted Cytotoxic T lymphocytes (CTL) epitopes Hpa525 (PAFSYSFFV), Hpa277 (KMLKSFLKA) and Hpa405 (WLSLLFKKL) from human heparanase could induce a potent anti-tumor immune response in vitro. The present study was designed to investigate whether the above peptides could induce immune responses in mice. Our results demonstrated that the effectors from heparanase peptide-immunized mice could effectively lyse various tumor cells that were heparanase positive and HLA-A*0201 matched. We also found that these peptide-specific CTLs did not lyse autologous lymphocytes that had low heparanase activity. Further study revealed that Hpa525, Hpa277, and Hpa405 peptides increased the frequency of IFN-gamma-producing T cells as compared to a negative peptide. These results suggest that Hpa525, Hpa277, and Hpa405 peptides are novel HLA-A*0201-restricted CTL epitopes capable of inducing heparanase-specific CTLs in mice. Because heparanase is expressed in most advanced malignant tumors, Hpa525, Hpa277, and Hpa405 peptide-based vaccines may be useful for the immunotherapy of patients with advanced tumors.
authors.affiliation: Institute of Gastroenterology, Southwest Hospital, Third Military Medical University, 400038, Chongqing, People's Republic of China.
authors.forename: Xu-Dong
authors.initials: XD
authors.lastname: Tang
authors.forename: Guang-Ping
authors.initials: GP
authors.lastname: Liang
authors.forename: Chuan
authors.initials: C
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Wan
authors.forename: Ting
authors.initials: T
authors.lastname: Chen
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.forename: Song-Tao
authors.initials: ST
authors.lastname: Yu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Xiong
authors.forename: Dian-Chun
authors.initials: DC
authors.lastname: Fang
authors.forename: Guo-Zheng
authors.initials: GZ
authors.lastname: Wang
authors.forename: Shi-Ming
authors.initials: SM
authors.lastname: Yang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005966:Glucuronidase / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology; D015789:HLA-A2 Antigen; D056945:Hep G2 Cells; D006801:Humans; D007114:Immunization / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology; D010455:Peptides / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D000099175:Heparanase
chemical_list: D018984:Epitopes, T-Lymphocyte; D005966:Glucuronidase; D015234:HLA-A Antigens; D015789:HLA-A2 Antigen; D007371:Interferon-gamma; D010455:Peptides; D000099175:Heparanase; C435939:HLA-A*02:01 antigen