title: Identification of a novel HLA-A2-restricted cytotoxic T lymphocyte epitope from cancer-testis antigen PLAC1 in breast cancer.
abstract: Identification of cytotoxic T lymphocyte (CTL) epitopes from tumor antigens is essential for the development of peptide vaccines against tumor immunotherapy. Among all the tumor antigens, the caner-testis (CT) antigens are the most widely studied and promising targets. PLAC1 (placenta-specific 1, CT92) was considered as a novel member of caner-testis antigen, which expressed in a wide range of human malignancies, most frequently in breast cancer. In this study, three native peptides and their analogues derived from PLAC1 were predicted by T cell epitope prediction programs including SYFPEITHI, BIMAS and NetCTL 1.2. Binding affinity and stability assays in T2 cells showed that two native peptides, p28 and p31, and their analogues (p28-1Y9 V, p31-1Y2L) had more potent binding activity towards HLA-A*0201 molecule. In ELISPOT assay, the CTLs induced by these four peptides could release IFN-γ. The CTLs induced by these four peptides from the peripheral blood mononuclear cells (PBMCs) of HLA-A*02+ healthy donor could lyse MCF-7 breast cancer cells (HLA-A*0201+, PLAC1+) in vitro. When immunized in HLA-A2.1/Kb transgenic mice, the peptide p28 could induce the most potent peptide-specific CTLs among these peptides. Therefore, our results indicated that the peptide p28 (VLCSIDWFM) could serve as a novel candidate epitope for the development of peptide vaccines against PLAC1-positive breast cancer.
authors.affiliation: Department of Bioengineering, Zhengzhou University, 100 Science Road, Zhengzhou, 450001, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Mingxia
authors.initials: M
authors.lastname: Zhai
authors.forename: Zongyin
authors.initials: Z
authors.lastname: Wu
authors.forename: Yuanming
authors.initials: Y
authors.lastname: Qi
authors.forename: Yahong
authors.initials: Y
authors.lastname: Wu
authors.forename: Chao
authors.initials: C
authors.lastname: Dai
authors.forename: Meng
authors.initials: M
authors.lastname: Sun
authors.forename: Lu
authors.initials: L
authors.lastname: Li
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Gao
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D045744:Cell Line, Tumor; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D005260:Female; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007114:Immunization; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000276:immunology*; D011257:Pregnancy Proteins / Q000737:chemistry / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013736:Testicular Neoplasms / Q000276:immunology* / Q000473:pathology; D022223:Vaccines, Subunit
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; C415583:PLAC1 protein, human; D010455:Peptides; D011257:Pregnancy Proteins; D022223:Vaccines, Subunit