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

✍ Scribed by Nobue Imai; Nanae Harashima; Masaaki Ito; Yoshiaki Miyagi; Mamoru Harada; Akira Yamada; Kyogo Itoh

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: French
• Weight: 132 KB
• Volume: 94
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.1461

✦ Synopsis

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-A24restricted 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.