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Identification of Lck‐derived peptides capable of inducing HLA‐A2‐restricted and tumor‐specific CTLs in cancer patients with distant metastases
Author(s) -
Imai Nobue,
Harashima Nanae,
Ito Masaaki,
Miyagi Yoshiaki,
Harada Mamoru,
Yamada Akira,
Itoh Kyogo
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.1461
Subject(s) - cytotoxic t cell , immunotherapy , cancer research , cancer , cancer immunotherapy , epitope , human leukocyte antigen , immunology , biology , antigen , medicine , immune system , in vitro , biochemistry
Abstract 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. © 2001 Wiley‐Liss, Inc.