Bodey Bela
Department of Pathology, Keck School of Medicine, University of Southern California, 8000-1 Canby Avenue, Reseda, CA 91335, USA.
Expert Opin Biol Ther. 2002 Aug;2(6):577-84. doi: 10.1517/14712598.2.6.577.
During the last decade, the aberrant expression of normal testicular proteins in neoplastically transformed cells became common knowledge. Cancer-testis antigens (CTAs) represent a novel family of immunogenic proteins. The genes MAGE, BAGE, GAGE, LAGE and NY-ESO-1 code for antigens that are recognised on various neoplastically transformed cells by autologous, cytolytic CD8 ( + ) T lymphocytes. The MAGE genes were initially analysed from melanomas and turned out to have an almost exclusively neoplasm specific expression pattern. In normal adult tissues, most 23 human MAGE genes are expressed only in the testis, with expression patterns suggesting that this gene family is involved in germ cell development. The SSX (synovial sarcoma on X chromosome) gene family, located on the X chromosome, encode a family of highly homologous nuclear proteins. A number of observations confirmed that all five SSX genes were expressed in normal testis. The newly detected CTA, NY-ESO-1, is regarded as one of the most immunogenic antigens ever isolated, inducing spontaneous host immune responses in 50% of patients with NY-ESO-1-expressing neoplasms. The identification of neoplasm-associated markers recognised by cellular or humoral effectors of the immune system has opened new perspectives for antigen directed, individualised antineoplastic immunotherapy. In preparation for this new era of targeted immunotherapy, a number of neoplasm-associated antigen families have been identified as targets for CD8+, cytolytic T lymphocytes in vitro and in vivo : (1) CTAs expressed in various neoplasms and in normal testis, restricted to male germ cells; (2) melanocyte differentiation antigens; (3) point mutations of normal genes; (4) antigens overexpressed in neoplastic tissues; and (5) viral antigens. Immunotherapeutic protocols directed against the CTAs have already been initiated to analyse the induction of antigen-specific cellular and humoral immune responses in vivo.
在过去十年中，正常睾丸蛋白在肿瘤转化细胞中的异常表达已成为常识。癌 - 睾丸抗原（CTA）代表了一类新的免疫原性蛋白家族。MAGE、BAGE、GAGE、LAGE和NY - ESO - 1基因编码的抗原可被自体细胞毒性CD8（+）T淋巴细胞识别，存在于各种肿瘤转化细胞上。MAGE基因最初是从黑色素瘤中分析得到的，结果显示其具有几乎完全肿瘤特异性的表达模式。在正常成人组织中，大多数23个人类MAGE基因仅在睾丸中表达，其表达模式表明该基因家族参与生殖细胞发育。位于X染色体上的SSX（X染色体上的滑膜肉瘤）基因家族编码一类高度同源的核蛋白。多项观察证实，所有五个SSX基因在正常睾丸中均有表达。新发现的CTA，NY - ESO - 1，被认为是迄今分离出的最具免疫原性的抗原之一，在50%表达NY - ESO - 1的肿瘤患者中可诱导自发的宿主免疫反应。免疫系统的细胞或体液效应因子所识别的肿瘤相关标志物的鉴定，为抗原导向的个体化抗肿瘤免疫治疗开辟了新的前景。为迎接这一靶向免疫治疗的新时代，已确定了多个肿瘤相关抗原家族作为体外和体内CD8 + 细胞毒性T淋巴细胞的靶点：（1）在各种肿瘤和正常睾丸中表达、局限于男性生殖细胞的CTA；（2）黑素细胞分化抗原；（3）正常基因的点突变；（4）在肿瘤组织中过表达的抗原；以及（5）病毒抗原。针对CTA的免疫治疗方案已经启动，以分析体内抗原特异性细胞免疫和体液免疫反应的诱导情况。
