Identification of Lck-derived peptides capable of inducing HLA-A2-restricted and tumor-specific CTLs in cancer patients with distant metastases

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Abstract
The Lck protein (p56lck), 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 Lck61–69, the Lck246–254, or the Lck422–430 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 Lck246–254 and Lck422–430 peptides could be useful for specific immunotherapy of HLA‐A2+ cancer patients, especially with distant metastases.