Department of Gynecological Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Future Oncol. 2010 May;6(5):717-32. doi: 10.2217/fon.10.36.
Cancer germline (CG; also known as cancer-testis) antigen genes are normally expressed in germ cells and trophoblast tissues and are aberrantly expressed in a variety of human malignancies. CG antigen genes have high clinical relevance as they encode a class of immunogenic and highly selective tumor antigens. CG antigen-directed immunotherapy is undergoing clinical evaluation for the treatment of a number of solid tumor malignancies and has been demonstrated to be safe, provoke immune responses and be of therapeutic benefit. Achieving an improved understanding of the mechanisms of CG antigen gene regulation will facilitate the continued development of targeted therapeutic approaches against tumors expressing these antigens. Substantial evidence suggests epigenetic mechanisms, particularly DNA methylation, as a primary regulator of CG antigen gene expression in normal and cancer cells as well as in stem cells. The roles of sequence-specific transcription factors and signal transduction pathways in controlling CG antigen gene expression are less clear but are emerging. A combinatorial therapeutic approach involving epigenetic modulatory drugs and CG antigen immunotherapy is suggested based on these data and is being actively pursued. In this article, we review the mechanisms of CG antigen gene regulation and discuss the implications of these mechanisms for the development of cancer immunotherapy approaches targeting CG antigens.
癌症种系（CG；也称为癌症-睾丸）抗原基因通常在生殖细胞和滋养层组织中表达，并且在多种人类恶性肿瘤中异常表达。CG 抗原基因具有很高的临床相关性，因为它们编码一类免疫原性和高度选择性的肿瘤抗原。CG 抗原导向的免疫疗法正在进行临床评估，用于治疗多种实体瘤恶性肿瘤，已被证明是安全的，可引发免疫反应并具有治疗益处。深入了解 CG 抗原基因调控的机制将有助于继续开发针对表达这些抗原的肿瘤的靶向治疗方法。大量证据表明，表观遗传机制，特别是 DNA 甲基化，是正常和癌细胞以及干细胞中 CG 抗原基因表达的主要调节因子。序列特异性转录因子和信号转导途径在控制 CG 抗原基因表达中的作用尚不清楚，但正在出现。基于这些数据，建议采用涉及表观遗传调节药物和 CG 抗原免疫疗法的组合治疗方法，并正在积极探索。本文综述了 CG 抗原基因调控的机制，并讨论了这些机制对开发针对 CG 抗原的癌症免疫治疗方法的意义。
