Identification of novel Lck-derived T helper epitope long peptides applicable for HLA-A2(+) cancer patients as cancer vaccine.

Abstract

The present study attempted to identify T helper epitope long peptides capable of inducing cytotoxic T lymphocytes (CTL) from Lck antigen (p56(Lck) ), the src family tyrosine kinase, which is known to be aberrantly expressed in metastatic cancers cells, in order to develop a long peptide-based cancer vaccine for HLA-A2(+) cancer patients. Based on the biding motif to the HLA-DR and HLA-A2 alleles, 94 peptides were prepared from the Lck antigen. These peptides were screened for their reactivity to immunoglobulin G (IgG) from plasma of cancer patients, followed by testing of their ability to induce both CD4(+) and CD8(+) T lymphocytes showing not only peptide-specific IFN-γ production but cytotoxicity against HLA-A2(+) cancer cells from peripheral blood mononuclear cells (PBMC) of HLA-A2(+) cancer patients. Among 94 peptides tested, the three T helper epitope long peptides and their inner CTL epitope short peptides with HLA-A2 binding motifs were frequently recognized by IgG of cancer patients, and efficiently induced both CD4(+) IFN-γ(+) and CD8(+) IFN-γ(+) T lymphocytes. Patients' PBMC stimulated with these long peptides showed cytotoxicity against HLA-A2(+) Lck(+) cancer cells in HLA-class I and HLA-class II dependent manners. These three peptides might be useful for long peptide-based vaccines for HLA-A2(+) cancer patients with Lck(+) tumor cells.

• Authors: Satoko Matsueda, Shigeki Shichijo, Sayaka Nagata, Chieko Seki, Akira Yamada, Masanori Noguchi, Kyogo Itoh
• Journal: Cancer science (Cancer Sci) Vol. 106 Issue 11 Pg. 1493-8 (Nov 2015) ISSN: 1349-7006 [Electronic] England
• PMID: 26331453 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Chemical References

• Antigens, Neoplasm
• Cancer Vaccines
• Epitopes, T-Lymphocyte
• HLA-A2 Antigen
• Peptides
• Lymphocyte Specific Protein Tyrosine Kinase p56(lck)

Topics

• Antigens, Neoplasm (immunology)
• Cancer Vaccines (immunology)
• Cell Line, Tumor
• Enzyme-Linked Immunosorbent Assay
• Enzyme-Linked Immunospot Assay
• Epitopes, T-Lymphocyte (immunology)
• Flow Cytometry
• HLA-A2 Antigen (immunology)
• Humans
• Lymphocyte Specific Protein Tyrosine Kinase p56(lck) (immunology)
• Neoplasms (immunology)
• Peptides (immunology)
• T-Lymphocytes, Helper-Inducer (immunology)