Identification of Lck-derived peptides capable of inducing HLA-A2-restricted and tumor-specific CTLs in cancer patients with distant metastases
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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DOI：
10.1002/ijc.1461
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发表时间：
2001-10-15
影响因子：
6.4
通讯作者：
Itoh, K
中科院分区：
文献类型：
--
作者：
Imai, N;Harashima, N;Itoh, K
Lck蛋白(pS6(Ick))是一种src家族酪氨酸激酶，对T细胞的发育和功能至关重要，在各种类型的癌症中都有异常表达。我们最近发现，Lck是一种肿瘤抗原，可被肿瘤转移患者的肿瘤特异性细胞趋化T淋巴细胞(CTL)识别。在这项研究中，我们试图确定能够在癌症患者中诱导人类白细胞抗原A2限制性和肿瘤特异性CTL的LCK衍生表位。2例人类白细胞抗原A2癌患者的肿瘤浸润性淋巴细胞(TIL)与HLAA0201、-A0206或A0207基因共转染COS-7细胞。这些TIL含有CTL，能够识别24种不同的多肽中的Lck(61-69)、Lck(246-254)或Lck(422-430)，这些多肽都是根据人类白细胞抗原A2结合基序制备的。重要的是，后两种多肽的体外致敏在有转移的人类白细胞抗原A2(+)癌症患者中诱导了肿瘤特异性CTL，但在那些没有转移的患者中没有。总之，Lck(246-254)和Lck(422-430)多肽可用于人类白细胞抗原A2(+)癌症患者的特异性免疫治疗，特别是有远处转移的患者。(C)2001年Wiley-Liss，Inc.
The Lck protein (pS6(Ick)), 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 cytotaxic 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 Ick 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 pepticles, 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. (C) 2001 Wiley-Liss, Inc.