The present study attempted to identify T helper epitope long peptides capable of inducing cytotoxic T lymphocytes (CTL) from Lck antigen (p56Lck), 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.
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