Mapping the HLA-A24-restricted T-cell epitope peptide from a tumour-associated antigen HER2 / neu: possible immunotherapy for colorectal carcinomas

Abstract

Summary HER2 / neu is a potential antigen candidate for immunotherapy because of its correlation to a poor prognosis and high expressions in many kinds of epithelial tumours. Especially in the colorectal carcinomas, the higher expression of HER2 / neu is recognized in metastatic regions as well as in primary sites. Several CTL epitopes restricted by HLA-A2.1 and -A3 were identified so far, however epitopes restricted by HLA-A24, that is one of the most common allele in Japanese and Caucasians, have not been identified. In this paper, we showed identification of a CTL epitope peptide of HER2 / neu restricted by HLA-A24. HLA-A24 binding peptides selected by an analysis based on HLA-A24 binding motifs were determined for their binding affinities to HLA-A24 molecules. The peptide with a sequence of RWGLLLALL (position 8-16) named HE1 showed the highest affinity. We induced CTLs from CD8 + cells of HLA-A24 healthy donors by stimulation with HE1-pulsed autologous dendritic cells. The CTLs showed cytotoxic activity against not only the peptide-pulsed target cells but also HLA-A24 colorectal tumour cell lines that endogenously overexpressed HER2 / neu. The antigen-specificity was confirmed by cold target inhibition assay using HE1-pulsed target cells. In summary, HER2 / neu peptide, RWGLLLALL, may contribute to the induction of antitumour immunity with the peptide-based immunotherapy for the colorectal carcinomas.

An efficient T-cell epitope discovery strategy using in silico prediction and the iTopia assay platform

“…For example, the well-known epitope CEA.24, 17 included as part of an epitope-based cancer vaccine in clinical development, 18 was 100% conserved in the proteins CEACAM1 and CEACAM6, which are expressed on normal cells 19 . The HLA-A2-restricted epitope CEA.233 9 and HLA-A3 restricted CEA.61 20 were found in CEACAM8 and CEACAM3, while the HLA-A24-restricted epitope HER2.907 21 was 100% conserved in the epidermal growth factor receptor (EGFR) and in HER3. The complete list of published CEA and HER2 T-cell epitopes found in other human proteins is provided in Table S1 .…”

Ring Finger Protein 43 as a New Target for Cancer Immunotherapy

“…Furthermore, several gene products, which had been already been known to be preferentially overexpressed by the tumor cells, have recently been shown to be recognized by CTLs as TAAs. These gene products include p53 (8), HER2/neu (9), and carcinoembryonic antigen (10). With antigenic epitope peptides derived from these TAAs, clinical trials have been initiated by multiple groups to treat cancer patients (11)(12)(13).…”

P53, hTERT, WT-1, and VEGFR2 are the most suitable targets for cancer vaccine therapy in HLA-A24 positive pancreatic adenocarcinoma

“…Recent technical advances have enabled the identification of various tumor-associated antigens (TAAs) [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21]; however, few of their epitopes are inducers of cytotoxic T lymphocyte (CTL) responses against tumors [22]. Several kinds of epitope have also been identified in patients with pancreatic adenocarcinoma [23,24].…”