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Abstract

A Human B cell Receptor Epitope-Based Erbb-2 Peptide (N: 163-182)with Pan-Reactivity to the T cells of Japanese Breast Cancer Patients

Banri Tsuda, Yoshie Kametani, Yumiko Goto, Yuki Saito, Yasuhiro Suzuki, Sonoko Habu, Hidetoshi Inoko and Yutaka Tokuda

Background: While monoclonal antibodies are widely accepted as being powerful in molecular targeting therapy, the activation of immunity by the B cell receptor epitope peptide has not been reported. Our objective was to evaluate a 20-mer multiple antigen peptide containing the anti-erbB-2 (HER2/neu) monoclonal antibody epitope (N: 163–182), designated as CH401MAP, as a general peptide vaccine for Japanese breast cancer patients. Methods: The 20-mer CH401 epitope peptide binding to the human leukocyte antigen (HLA) of Japanese breast cancer patients was predicted by algorithms from the following databases: SYFPEITHI, Bioinformatics and Molecular Analysis Section (BIMAS), and Immune Epitope Database (IEDB). Peripheral blood mononuclear cells (PBMCs) were collected from 173 breast cancer patients and stimulated with the peptide in vitro. Cytokine secretion was examined by enzyme-linked immunosorbent assay (ELISA). Flow cytometric analysis was performed to detect CD4 and CD8 T cells and Treg cells. Results: Using the algorithms used for the simulation, CH401MAP was predicted to bind to more than 90% of class I HLAs and to 30–50% of class II HLAs in breast cancer patients. In vitro stimulation of patients’ PBMCs with CH401MAP induced a significant increase in interleukin-2 secretion, proliferation, and CD8 T cell ratios. Conclusions: Our study demonstrates that CH401MAP induces T cell activation in PBMCs derived from breast cancer patients. This antibody epitope-based peptide with HLA motifs could be a candidate peptide vaccine for general breast cancer.