Chen Y T, Scanlan M J, Sahin U, Türeci O, Gure A O, Tsang S, Williamson B, Stockert E, Pfreundschuh M, Old L J
Cornell University Medical College, New York, NY 10021, USA.
Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1914-8. doi: 10.1073/pnas.94.5.1914.
Serological analysis of recombinant cDNA expression libraries (SEREX) using tumor mRNA and autologous patient serum provides a powerful approach to identify immunogenic tumor antigens. We have applied this methodology to a case of esophageal squamous cell carcinoma and identified several candidate tumor targets. One of these, NY-ESO-1, showed restricted mRNA expression in normal tissues, with high-level mRNA expression found only in testis and ovary tissues. Reverse transcription-PCR analysis showed NY-ESO-1 mRNA expression in a variable proportion of a wide array of human cancers, including melanoma, breast cancer, bladder cancer, prostate cancer, and hepatocellular carcinoma. NY-ESO-1 encodes a putative protein of Mr 17,995 having no homology with any known protein. The pattern of NY-ESO-1 expression indicates that it belongs to an expanding family of immunogenic testicular antigens that are aberrantly expressed in human cancers in a lineage-nonspecific fashion. These antigens, initially detected by either cytotoxic T cells (MAGE, BAGE, GAGE-1) or antibodies [HOM-MEL-40(SSX2), NY-ESO-1], represent a pool of antigenic targets for cancer vaccination.
利用肿瘤信使核糖核酸(mRNA)和患者自身血清对重组互补脱氧核糖核酸(cDNA)表达文库进行血清学分析(SEREX),为鉴定免疫原性肿瘤抗原提供了一种强有力的方法。我们已将此方法应用于一例食管鳞状细胞癌病例,并鉴定出了几个候选肿瘤靶点。其中之一,NY-ESO-1,在正常组织中mRNA表达受限,仅在睾丸和卵巢组织中发现高水平的mRNA表达。逆转录-聚合酶链反应(RT-PCR)分析显示,NY-ESO-1 mRNA在多种人类癌症中均有不同比例的表达,包括黑色素瘤、乳腺癌、膀胱癌、前列腺癌和肝细胞癌。NY-ESO-1编码一种推定的蛋白质,其分子量为17,995,与任何已知蛋白质均无同源性。NY-ESO-1的表达模式表明,它属于一个不断扩大的免疫原性睾丸抗原家族,这些抗原在人类癌症中以谱系非特异性方式异常表达。这些抗原最初是通过细胞毒性T细胞(MAGE、BAGE、GAGE-1)或抗体[HOM-MEL-40(SSX2)、NY-ESO-1]检测到的,代表了癌症疫苗接种的一组抗原靶点。