Journal Article

Identification of a novel HLA-A2-restricted cytotoxic T lymphocyte epitope from cancer-testis antigen PLAC1 in breast cancer

Qi, Yuanming, Sun, Meng, Wu, Yahong, Liu, Wei, Wu, Zongyin, Dai, Chao, Li, Lu, Zhai, Mingxia, Gao, Yanfeng

2012

Overview

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/K b 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.

• Publisher: Springer Vienna,Springer Nature B.V
• Subject: Amino Acid Sequence / Analytical Chemistry / Animals / Antigen (tumor-associated) / Antigens / Antigens, Neoplasm - genetics / Antigens, Neoplasm - immunology / Binding / Biochemical Engineering / Biochemistry / Biomedical and Life Sciences / Breast cancer / Breast Neoplasms - immunology / Breast Neoplasms - pathology / Breast Neoplasms - prevention & control / Cancer vaccines / Cancer Vaccines - administration & dosage / Cancer Vaccines - chemistry / Cancer Vaccines - immunology / Cell Line, Tumor / Cytotoxicity / Enzyme-linked immunosorbent assay / Epitopes / Epitopes, T-Lymphocyte - genetics / Epitopes, T-Lymphocyte - immunology / Female / Histocompatibility antigen HLA / HLA-A2 Antigen - genetics / HLA-A2 Antigen - immunology / Humans / Immunization / Immunotherapy / Leukocytes (mononuclear) / Life Sciences / Lymphocytes / Lymphocytes T / Male / Malignancy / Mice / Molecular Sequence Data / Neurobiology / Original Article / Peptides / Peptides - administration & dosage / Peptides - chemical synthesis / Peptides - immunology / Peripheral blood mononuclear cells / Placenta / Predictions / Pregnancy Proteins - chemistry / Pregnancy Proteins - immunology / Proteomics / T-Lymphocytes, Cytotoxic - immunology / Testicular Neoplasms - immunology / Testicular Neoplasms - pathology / Transgenic mice / Tumors / Vaccines / Vaccines, Subunit / γ-Interferon