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.

PLAC1-specific TCR-engineered T cells mediate antigen-specific antitumor effects in breast cancer

“…Thus, the immune responses directed against CTAs by PLAC1 are unlikely to result in the recognition of these tissues. In addition, HLA-A * 0201 is the most widely expressed HLA-I molecule in the Chinese population (34). Therefore, the identification of HLA-A * 0201-restricted and PLAC1-specific TCR-engineered T cells would be critical to the immunotherapy of breast cancer; however, it has not yet been well-studied.…”

“…Liu et al (34) demonstrated that the HLA-A * 0201-restricted T cell epitope, PLAC1 28-36 -peptide (VLCSIDWFM), may induce the most potent peptide-specific CTLs and serve as a novel candidate epitope for the development of peptide vaccines against PLAC1-positive breast cancer. In the present study, CTL clones against PLAC1 (VLCSIDWFM) were additionally isolated successfully.…”

In Silico Analysis of Epitope-Based Vaccine Candidates against Hepatitis B Virus Polymerase Protein

“…In vitro assay indicated that CTLs induced by these epitopes from peripheral blood mononuclear cells (PBMCs) could release IFN-γ and lyse MCF-7 breast cancer cells. In vivo assay also proved that epitope p28 of PLAC1 could induce specific CTLs [71]. Moreover, epidermal growth factor receptor pathway substrate 8 (EPS8) is overexpressed in most human tumor tissue, while expressed to a lesser degree in normal tissue.…”

Identification and Validation of Targets for Cancer Immunotherapy: From the Bench-to-Bedside

“…Amino acids that are considered as having an adverse effect on binding have a coefficient of -1 to -3 [60]. SYFPEITHI database gets updated regularly and has been used to identify various ligands; p28 peptide as an epitope for the CT antigen PLAC1 in breast cancer [61], p101-111 is the first CTA-derived peptide which induces CD4(+), CD8(+), and B-cell responses in vitro [62], p43-57 epitope stimulates T cells in HCA587-derived tumours [63] and PASD1(1) -PASD1(5) [51].…”