Identification of Lck-derived peptides capable of inducing HLA-A2-restricted and tumor-specific CTLs in cancer patients with distant metastases.
The Lck protein (p56(lck)), a src family tyrosine kinase essential for T cell development and function, is aberrantly expressed in various types of cancers. We revealed recently that Lck can be a tumor antigen recognized by HLA-A24-restricted and tumor-specific cytotoxic T lymphocytes (CTLs) of cancer patients with metastases. In this study, we tried to identify Lck-derived epitopes capable of inducing HLA-A2-restricted and tumor-specific CTLs in cancer patients. The tumor-infiltrating lymphocytes (TILs) from 2 HLA-A2 cancer patients were found to respond to COS-7 cells when co-transfected with the lck gene and either HLA-A0201, -A0206, or A0207 cDNA. These TILs contained CTLs capable of recognizing either the Lck(61-69), the Lck(246-254), or the Lck(422-430) peptide among 24 different peptides, all of which were prepared based on the HLA-A2 binding motif. Importantly, in vitro sensitization with the latter 2 peptides induced tumor-specific CTLs in HLA-A2(+) cancer patients with metastases, but not in those without metastases. Overall, the Lck(246-254) and Lck(422-430) peptides could be useful for specific immunotherapy of HLA-A2(+) cancer patients, especially with distant metastases.
Imai
N
N
Cancer Vaccine Development Division, Kurume University Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
Harashima
N
N
Ito
M
M
Miyagi
Y
Y
Harada
M
M
Yamada
A
A
Itoh
K
K
D000818:Animals; D019556:COS Cells; D019496:Cancer Vaccines / Q000276:immunology*; D006224:Cricetinae; D015789:HLA-A2 Antigen / Q000032:analysis / Q000235:genetics*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000494:pharmacology*; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000628:therapy*; D010446:Peptide Fragments / Q000494:pharmacology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D019496:Cancer Vaccines; D015789:HLA-A2 Antigen; D010446:Peptide Fragments; D007371:Interferon-gamma; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)