title: Peptide FLNPDVLDI of heparanase is a novel HLA-A2-restricted CTL epitope and elicits potent immunological antitumor effects in vitro with an 8-branched design.
abstract: The aim of this study was to predict and characterize a novel HLA-A2-restricted T-cell epitope of the human heparanase (HPSE) protein, as well as to evaluate its antitumor immunological effects in vitro with an 8-branched multiple antigenic peptide (MAP) design. The amino acid sequence of HPSE was scanned, and the cytotoxic T lymphocyte (CTL) epitopes were predicted using HLA-A2-restricted epitope-predictive algorithms based on supermotif and quantitative motif methods. The affinity of candidate peptides to HLA-A2 was evaluated using peptide-binding assay, by virtue of the characteristics of T2 cells. The MAPs consisting of the selected peptides were synthesized using an 8-branched design. The specific CTL-inducing ability of the MAPs was assessed by LDH release assay, and the CTL activity was evaluated by INF-γ ELISPOT assay. Among the predicted nonapeptides, the FLNPDVLDI peptide of HPSE showed the highest affinity to the HLA-A2 molecule. The 8-branched MAP comprising FLNPDVLDI induced specific CTLs for human HPSE in vitro, which effectively secreted IFN-γ and potently lysed HCC97-H human hepatocarcinoma cells and SW-480 human colonic carcinoma cells. The nonapeptide FLNPDVLDI of human HPSE appears to be a novel HLA-A2-restricted CTL epitope, and its 8-branch designed MAP is capable of inducing a potent HPSE-specific CTL response against tumor cells in vitro. Our study provides theoretical evidence for the peptide-based antitumor immunotherapy.
authors.affiliation: Department of Gastroenterology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Jianmin
authors.initials: J
authors.lastname: Yang
authors.forename: Daiming
authors.initials: D
authors.lastname: Fan
authors.forename: Houquan
authors.initials: H
authors.lastname: Tao
authors.forename: Huiju
authors.initials: H
authors.lastname: Wang
authors.forename: Tong
authors.initials: T
authors.lastname: Yu
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology*; D000970:Antineoplastic Agents / Q000276:immunology*; D002277:Carcinoma / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000276:immunology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005966:Glucuronidase / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007371:Interferon-gamma / Q000276:immunology; D008113:Liver Neoplasms / Q000276:immunology; D010455:Peptides / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D000099175:Heparanase
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D000939:Epitopes; D018984:Epitopes, T-Lymphocyte; D005966:Glucuronidase; D015789:HLA-A2 Antigen; D007371:Interferon-gamma; D010455:Peptides; D000099175:Heparanase