HLA-A2-restricted CTL epitopes of a novel lung cancer-associated cancer testis antigen, cell division cycle associated 1, can induce tumor-reactive CTL
HLA-A2-restricted CTL epitopes of a novel lung cancer-associated cancer testis antigen, cell division cycle associated 1, can induce tumor-reactive CTL
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DOI：
10.1002/ijc.23823
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发表时间：
2008-12-01
影响因子：
6.4
通讯作者：
Nishimura, Yasuharu
中科院分区：
文献类型：
--
作者：
Harao, Michiko;Hirata, Shinya;Nishimura, Yasuharu
为了开发一种新的癌症免疫疗法，我们之前已经鉴定了几种肿瘤相关抗原（TAAs）和人类组织相容性白细胞(HLA)-A2/ a24限制性细胞毒性T淋巴细胞（CTL）识别的表位。在本研究中，我们试图鉴定肺癌（I、C）的TAA及其HLA-A2限制性CTL。表位为肝癌免疫治疗提供有用的靶抗原。我们使用cDNA微阵列分析鉴定了在非小细胞U中过表达的新型睾丸癌抗原——细胞分裂周期相关基因I （CDCA1）。CDCA1在大多数小细胞肝癌、胆管细胞癌、普通膀胱癌和肾细胞癌中的表达水平均升高。我们利用HLA-A2.1转基因小鼠鉴定了小鼠CTL识别的HLA-A2 （A*0201）限制性CDCA1表位，并研究了这些肽是否能从HLA-A2阳性供者和非小细胞肺癌患者的外周血单核细胞（PBMCs）中诱导CDCA1反应性CTL。因此，我们发现CDCA1(65-73) （YMMPVNSEV）肽和CDCA1(351-359) （KLATAQFKI）肽可以在HLA-A2.1转基因小鼠中诱导肽反应性ctl。适合HLA-A2供体，用这些肽在体外刺激PBMC可以诱导肽反应性ctl，杀死内源性表达HLA-A2和CDCA1的肿瘤细胞系。因此，CDCA1是一种在LC中过表达的新型睾丸癌抗原。胆管细胞癌、膀胱癌和肾细胞癌，因此CDCA1可能是一种理想的TAA，可用于这些癌症的诊断和免疫治疗。(C) 2008 Wiley-Liss, Inc。
Toward the development of a novel cancer immunotherapy, we have previously identified several tumor-associated antigens (TAAs) and the epitopes recognized by human histocompatibility leukocyte (HLA)-A2/A24-restricted cytotoxic T lymphocyte (CTL). In this study, we tried to identify a TAA of lung cancer (I.,C) and its HLA-A2 restricted CTL. epitopes to provide a target antigen useful for cancer immunotherapy of LC. We identified it novel cancer testis antigen, cell division cycle associated gene I (CDCA1), overexpressed in nonsmall cell U: using a cDNA microarray analysis. The expression levels of CDCA1 were also increased in the majority of small cell LIE, cholangiocellular cancer, uninary bladder cancer and renal cell cancers. We used HLA-A2.1 transgenic mice to identify the HLA-A2 (A*0201)- restricted CDCA1 epitopes recognized by niouse CTL, and we investigated whether these peptides could induce CDCA1-reactive CTLs from the peripheral blood mononuclear cells (PBMCs) of HLA-A2-positive donors and a NSCLC patient. Consequently, we found that the CDCA1(65-73) (YMMPVNSEV) peptide and CDCA1(351-359) (KLATAQFKI) peptide could induce peptide-reactive CTLs in HLA-A2.1 transgenic mice. fit HLA-A2 donors, in vitro stimulation of PBMC with these peptides could induce peptide-reactive CTLs which killed tumor cell lines endogenously expressing both HLA-A2 and CDCA1. As a result, CDCA1 is a novel cancer-testis antigen overexpressed in LC. cholangiocellular cancer, urinary bladder cancer and renal cell cancers, and CDCA1 may therefore be an ideal TAA useful for the diagnosis and immunotherapy of these cancers. (C) 2008 Wiley-Liss, Inc.