Identification of a novel human cancer/testis antigen, KM-HN-1, recognized by cellular and humoral immune responses
Identification of a novel human cancer/testis antigen, KM-HN-1, recognized by cellular and humoral immune responses
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DOI：
10.1158/1078-0432.ccr-04-0475
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发表时间：
2004-09-15
影响因子：
11.5
通讯作者：
Nishimura, Y
中科院分区：
文献类型：
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作者：
Monji, M;Nakatsura, T;Nishimura, Y
目的：我们利用人睾丸cDNA表达文库的血清学筛选来鉴定在癌症患者中引起体液和细胞免疫应答的新的癌症/睾丸抗原。实验设计和结果：我们鉴定了一种新的基因命名为KH-HN-1，其表达在正常组织中是睾丸特异性的;它含有卷曲螺旋结构域和亮氨酸拉链基序，并编码由833个氨基酸组成的推定蛋白质。在各种癌组织和癌细胞系中观察到KM-HN-1在mRNA和蛋白质水平上的表达。食管癌细胞系的免疫荧光染色显示，在有丝分裂过程中，KM-HN-1蛋白只存在于细胞核中。制备重组KM-HN-1蛋白，并用于ELISA以定量对KM-HN-1特异性的IgG抗体的水平。在许多类型和数量的癌症患者中检测到较高水平的特异性KM-HN-1 IgG抗体，但在健康供体中未检测到。从HLA-A*2402阳性健康供体和癌症患者产生的对KM-HN-1特异的CTL系杀死表达KM-HN-1的人类白细胞抗原（HLA）-A24阳性癌细胞，但不杀死不表达KM-HN-1或HLA-A24的细胞系。我们发现了一种新的癌症/睾丸抗原，KM-HN-1，它在各种类型的癌症患者中引起体液免疫反应。此外，KM-HN-1特异性CTL可以从健康供体和癌症患者中产生，这表明KM-HN-1可以成为癌症免疫治疗的理想靶点。
Purpose: We used serologic screening of a cDNA expression library of human testis to identify novel cancer/ testis antigens that elicit both humoral and cellular immune responses in cancer patients.Experimental Design and Results: We identified a novel gene designated KH-HN-1 the expression of which is testis-specific among, normal tissues; it contains coiled coil domains and a leucine zipper motif and encodes a putative protein consisting of 833 amino acids. KM-HN-1 expression was observed in various cancer tissues and cancer cell lines at both mRNA and protein levels. Inummofluorescence staining of an esophageal cancer cell line revealed that KM-HN-1 protein was present exclusively in the nucleus during mitosis. Recombinant KM-HN-1 protein was produced, and used for ELISA to quantitate levels of IgG antibody specific to KM-HN-1. Higher levels of IgG antibodies specific to KM-HN-1 were detected in many types and numbers of cancer patients but not in healthy donors. The CTL lines specific to KM-HN-1, generated from HLA-A*2402-positive healthy donors and cancer patients, killed human leukocyte antigen (HLA)-A24-positive cancer cells expressing KM-HN-1 but not cell lines that did not express either KM-HN-1 or HLA-A24.Conclusions: We identified a novel cancer/testis antigen, KM-HN-1, which elicited humoral immune responses in patients with various types of cancer. Furthermore, KM-HN-1-specific CTLs could be generated from both healthy donors and cancer patients, which indicated that KM-HN-1 can be a candidate for an ideal target for cancer immunotherapy.