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

Amino Acids. 2012 Jun;42(6):2257-65. doi: 10.1007/s00726-011-0966-3. Epub 2011 Jun 28.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology
  • Breast Neoplasms / immunology
  • Breast Neoplasms / pathology
  • Breast Neoplasms / prevention & control*
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / chemistry
  • Cancer Vaccines / immunology*
  • Cell Line, Tumor
  • Epitopes, T-Lymphocyte / genetics
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • HLA-A2 Antigen / genetics
  • HLA-A2 Antigen / immunology*
  • Humans
  • Immunization
  • Male
  • Mice
  • Molecular Sequence Data
  • Peptides / administration & dosage
  • Peptides / chemical synthesis
  • Peptides / immunology*
  • Pregnancy Proteins / chemistry
  • Pregnancy Proteins / immunology*
  • T-Lymphocytes, Cytotoxic / immunology
  • Testicular Neoplasms / immunology*
  • Testicular Neoplasms / pathology
  • Vaccines, Subunit

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines
  • Epitopes, T-Lymphocyte
  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • PLAC1 protein, human
  • Peptides
  • Pregnancy Proteins
  • Vaccines, Subunit