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

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.