University of Washington, Spokane, Washington, USA.
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
J Immunother Cancer. 2021 Jun;9(6). doi: 10.1136/jitc-2020-002072.
Synovial sarcoma (SS) is a rare cancer that disproportionately affects children and young adults. Cancer testis antigens (CTAs) are proteins that are expressed early in embryonic development, but generally not expressed in normal tissue. They are aberrantly expressed in many different cancer types and are an attractive therapeutic target for immunotherapies. CTAs are expressed at high levels in SS. This high level of CTA expression makes SS an ideal cancer for treatment strategies aimed at harnessing the immune system to recognize aberrant CTA expression and fight against the cancer. Pivotal clinical trials are now underway, with the potential to dramatically alter the landscape of SS management and treatment from current standards of care. In this review, we describe the rationale for targeting CTAs in SS with a focus on NY-ESO-1 and MAGE-A4, the current state of vaccine and T-cell receptor-based therapies, and consider emerging opportunities for future development.
滑膜肉瘤(SS)是一种罕见的癌症,在儿童和青年中发病率较高。癌症睾丸抗原(CTA)是在胚胎早期表达的蛋白质,但通常不在正常组织中表达。它们在许多不同的癌症类型中异常表达,是免疫疗法的一个有吸引力的治疗靶点。CTA 在 SS 中高表达。这种高水平的 CTA 表达使 SS 成为一种理想的癌症,可用于治疗策略,旨在利用免疫系统识别异常的 CTA 表达并对抗癌症。关键性临床试验正在进行中,有可能从当前的护理标准显著改变 SS 的管理和治疗格局。在这篇综述中,我们描述了用 NY-ESO-1 和 MAGE-A4 作为 SS 中 CTA 的靶向治疗的基本原理,重点介绍了疫苗和 T 细胞受体为基础的治疗的现状,并考虑了未来发展的新机遇。