Identification of Lck-derived peptides applicable to anti-cancer vaccine for patients with human leukocyte antigen-A3 supertype alleles.
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.
Department of Immunology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan. haramano@med.shimane-u.ac.jp
M
M
Naito
Y
Y
Komohara
Y
Y
Ishihara
M
M
Noguchi
Y
Y
Yamashita
T
T
Shirakusa
A
A
Yamada
K
K
Itoh
M
M
Harada
D019496:Cancer Vaccines / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D015791:HLA-A3 Antigen / Q000235:genetics*; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000276:immunology*; D008297:Male; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D010455:Peptides; D011471:Prostatic Neoplasms / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D019496:Cancer Vaccines; D015791:HLA-A3 Antigen; D007074:Immunoglobulin G; D010455:Peptides; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)