Identification of novel L ck‐derived T helper epitope long peptides applicable for HLA ‐ A 2 + cancer patients as cancer vaccine

The present study attempted to identify T helper epitope long peptides capable of inducing cytotoxic T lymphocytes ( CTL ) from L ck 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 ‐ A 2 + cancer patients. Based on the biding motif to the HLA ‐ DR and HLA ‐ A 2 alleles, 94 peptides were prepared from the L ck antigen. These peptides were screened for their reactivity to immunoglobulin G ( I g G ) from plasma of cancer patients, followed by testing of their ability to induce both CD 4 + and CD 8 + T lymphocytes showing not only peptide‐specific IFN ‐γ production but cytotoxicity against HLA ‐ A 2 + cancer cells from peripheral blood mononuclear cells ( PBMC ) of HLA ‐ A 2 + cancer patients. Among 94 peptides tested, the three T helper epitope long peptides and their inner CTL epitope short peptides with HLA ‐ A 2 binding motifs were frequently recognized by I g G of cancer patients, and efficiently induced both CD 4 + IFN ‐γ + and CD 8 + IFN ‐γ + T lymphocytes. Patients' PBMC stimulated with these long peptides showed cytotoxicity against HLA ‐ A 2 + L ck + 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 ‐ A 2 + cancer patients with L ck + tumor cells.