Abstract
The identification of peptide vaccine candidates to date has been focused on human leukocyte antigen (HLA)-A2 and -A24 alleles. In this study, we attempted to identify cytotoxic T lymphocyte (CTL)-directed Lck-derived peptides applicable to HLA-A11(+), -A31(+), or -A33(+) cancer patients, because these HLA-A alleles share binding motifs, designated HLA-A3 supertype alleles, and because the Lck is preferentially expressed in metastatic cancer. Twenty-one Lck-derived peptides were prepared based on the binding motif to the HLA-A3 supertype alleles. They were first screened for their recognisability by immunoglobulin G (IgG) in the plasma of prostate cancer patients, and the selected candidates were subsequently tested for their potential to induce peptide-specific CTLs from peripheral blood mononuclear cells of HLA-A3 supertype(+) cancer patients. As a result, four Lck peptides were frequently recognised by IgGs, and three of them - Lck(90-99), Lck(449-458), and Lck(450-458) - efficiently induced peptide-specific and cancer-reactive CTLs. Their cytotoxicity towards cancer cells was mainly ascribed to HLA class I-restricted and peptide-specific CD8(+) T cells. These results indicate that these three Lck peptides are applicable to HLA-A3 supertype(+) cancer patients, especially those with metastasis. This information could facilitate the development of peptide-based anti-cancer vaccine for patients with alleles other than HLA-A2 and -A24.