Cancer Research Center, Qatar Biomedical Research Institute, Qatar Foundation, Hamad Bin Khalifa University, Doha, Qatar.
Immunology, Inflammation, and Metabolism Department, Tumor Biology, Immunology, and Therapy Section, Division of Translational Medicine, Sidra Medicine, Doha, Qatar.
Front Immunol. 2018 May 1;9:947. doi: 10.3389/fimmu.2018.00947. eCollection 2018.
NY-ESO-1 or New York esophageal squamous cell carcinoma 1 is a well-known cancer-testis antigen (CTAs) with re-expression in numerous cancer types. Its ability to elicit spontaneous humoral and cellular immune responses, together with its restricted expression pattern, have rendered it a good candidate target for cancer immunotherapy. In this review, we provide background information on NY-ESO-1 expression and function in normal and cancerous tissues. Furthermore, NY-ESO-1-specific immune responses have been observed in various cancer types; however, their utility as biomarkers are not well determined. Finally, we describe the immune-based therapeutic options targeting NY-ESO-1 that are currently in clinical trial. We will highlight the recent advancements made in NY-ESO-1 cancer vaccines, adoptive T cell therapy, and combinatorial treatment with checkpoint inhibitors and will discuss the current trends for future NY-ESO-1 based immunotherapy. Cancer treatment has been revolutionized over the last few decades with immunotherapy emerging at the forefront. Immune-based interventions have shown promising results, providing a new treatment avenue for durable clinical responses in various cancer types. The majority of successful immunotherapy studies have been reported in liquid cancers, whereas these approaches have met many challenges in solid cancers. Effective immunotherapy in solid cancers is hampered by the complex, dynamic tumor microenvironment that modulates the extent and phenotype of the antitumor immune response. Furthermore, many solid tumor-associated antigens are not private but can be found in normal somatic tissues, resulting in minor to detrimental off-target toxicities. Therefore, there is an ongoing effort to identify tumor-specific antigens to target using various immune-based modalities. CTAs are considered good candidate targets for immunotherapy as they are characterized by a restricted expression in normal somatic tissues concomitant with a re-expression in solid epithelial cancers. Moreover, several CTAs have been found to induce a spontaneous immune response, NY-ESO-1 being the most immunogenic among the family members. Hence, this review will focus on NY-ESO-1 and discuss the past and current NY-ESO-1 targeted immunotherapeutic strategies.
NY-ESO-1 或纽约食管鳞状细胞癌 1 是一种众所周知的癌症睾丸抗原(CTA),在许多癌症类型中重新表达。它能够引发自发的体液和细胞免疫反应,加上其受限的表达模式,使其成为癌症免疫治疗的良好候选靶点。在这篇综述中,我们提供了 NY-ESO-1 在正常和癌变组织中的表达和功能的背景信息。此外,在各种癌症类型中观察到了针对 NY-ESO-1 的特异性免疫反应;然而,它们作为生物标志物的效用尚未确定。最后,我们描述了目前正在临床试验中的针对 NY-ESO-1 的免疫治疗选择。我们将重点介绍 NY-ESO-1 癌症疫苗、过继性 T 细胞疗法以及与检查点抑制剂联合治疗方面的最新进展,并讨论未来基于 NY-ESO-1 的免疫治疗的当前趋势。在过去的几十年中,癌症治疗发生了革命性的变化,免疫疗法成为了前沿。免疫干预已经显示出了有希望的结果,为各种癌症类型提供了持久的临床反应的新治疗途径。大多数成功的免疫治疗研究都在液体癌症中报道,而这些方法在实体癌症中遇到了许多挑战。有效的免疫治疗在实体癌症中受到复杂、动态的肿瘤微环境的阻碍,这种微环境调节了抗肿瘤免疫反应的程度和表型。此外,许多与实体肿瘤相关的抗原不是独特的,而是可以在正常的体细胞组织中发现,导致轻微到有害的脱靶毒性。因此,人们正在努力识别肿瘤特异性抗原,以便使用各种免疫方法进行靶向治疗。CTA 被认为是免疫治疗的良好候选靶点,因为它们的特征是在正常的体细胞组织中表达受限,同时在实体上皮癌中重新表达。此外,已经发现一些 CTA 能够诱导自发的免疫反应,其中 NY-ESO-1 是家族成员中最具免疫原性的。因此,本综述将重点讨论 NY-ESO-1,并讨论过去和当前针对 NY-ESO-1 的免疫治疗策略。