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.