Lim Seah H, Zhang Yana, Zhang Jian
Amarillo Blood and Marrow Transplant Program, Texas Oncology-Amarillo, Cancer Center TX, USA.
Am J Blood Res. 2012;2(1):29-35. Epub 2012 Jan 1.
Immunotherapy is theoretically an attractive therapeutic option for patients with hematological malignancies. Various laboratory studies suggested the importance of the choice of tumor antigen for successful immunotherapy. Cancer-testis antigens (CTAs) are potentially suitable molecules for tumor vaccines of hematological malignancies because of their high immunogenicity in vivo, even in cancer-bearing patients, and their relatively restricted normal tissue distribution. Tumor cell kill using a CTA-based immunotherapy will, therefore, be more specific and associated with less toxicities when compared to chemotherapy. Many CTAs have been identified in various hematologic malignancies. In this review, we will take the readers through the journey of hopes and the disappointments arisen from the discovery of CTAs. We will describe the features of CTAs and their expression in hematologic malignancies. We will also discuss the mechanisms regulating the expression of these CTAs, from a primary regulatory mechanism involving DNA methylation to secondary controls by cytokines. Finally, we will address the potential obstacles that will prevent the successful use of CTAs as targets for tumor immunotherapy.
从理论上讲,免疫疗法对于血液系统恶性肿瘤患者是一种颇具吸引力的治疗选择。各种实验室研究表明,选择肿瘤抗原对于成功的免疫治疗至关重要。癌-睾丸抗原(CTA)因其在体内具有高免疫原性,即使在癌症患者中也是如此,且其正常组织分布相对受限,所以有可能是血液系统恶性肿瘤肿瘤疫苗的合适分子。因此,与化疗相比,使用基于CTA的免疫疗法杀伤肿瘤细胞将更具特异性且毒性更小。在各种血液系统恶性肿瘤中已鉴定出许多CTA。在本综述中,我们将带领读者经历CTA发现过程中的希望与失望之旅。我们将描述CTA的特征及其在血液系统恶性肿瘤中的表达。我们还将讨论调节这些CTA表达的机制,从涉及DNA甲基化的主要调节机制到细胞因子的二级调控。最后,我们将探讨阻碍CTA成功用作肿瘤免疫治疗靶点的潜在障碍。