HLA-A2-restricted cytotoxic T lymphocyte epitopes from human heparanase as novel targets for broad-spectrum tumor immunotherapy.

Neoplasia : an International Journal for Oncology Research
Ting ChenShi-Ming Yang

Abstract

Peptide vaccination for cancer immunotherapy requires identification of peptide epitopes derived from antigenic proteins associated with tumors. Heparanase (Hpa) is broadly expressed in various advanced tumors and seems to be an attractive new tumor-associated antigen. The present study was designed to predict and identify HLA-A2-restricted cytotoxic T lymphocyte (CTL) epitopes in the protein of human Hpa. For this purpose, HLA-A2-restricted CTL epitopes were identified using the following four-step procedure: 1) a computer-based epitope prediction from the amino acid sequence of human Hpa, 2) a peptide-binding assay to determine the affinity of the predicted protein with the HLA-A2 molecule, 3) stimulation of the primary T-cell response against the predicted peptides in vitro, and 4) testing of the induced CTLs toward different kinds of carcinoma cells expressing Hpa antigens and/or HLA-A2. The results demonstrated that, of the tested peptides, effectors induced by peptides of human Hpa containing residues 525-533 (PAFSYSFFV, Hpa525), 277-285 (KMLKSFLKA, Hpa277), and 405-413 (WLSLLFKKL, Hpa405) could effectively lyse various tumor cell lines that were Hpa-positive and HLA-A2-matched. We also found that these peptide-specific C...Continue Reading

Citations

Feb 26, 2010·Cancer Immunology, Immunotherapy : CII·Xu-Dong TangShi-Ming Yang
Apr 8, 2016·Human Vaccines & Immunotherapeutics·Gil ArvatzIsrael Vlodavsky
Sep 11, 2018·Frontiers in Endocrinology·Arvindhan NagarajanNarendra Wajapeyee
May 22, 2019·Frontiers in Oncology·Alyce J MayfoshMark D Hulett
May 31, 2020·International Journal of Molecular Sciences·Yoshihiro TatsumiKiyohide Fujimoto
Aug 4, 2011·Cancer Microenvironment : Official Journal of the International Cancer Microenvironment Society·Israel VlodavskyMichael Elkin
Jun 12, 2013·Journal of Neuro-oncology·Zhao YangQingwu Yang
Jul 25, 2019·Seminars in Cancer Biology·Nancy A Espinoza-Sánchez, Martin Götte

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