Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
J Med Chem. 2022 Sep 22;65(18):11900-11912. doi: 10.1021/acs.jmedchem.2c00803. Epub 2022 Sep 9.
Blockade of cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) has produced considerable therapeutic effect, but only in a fraction of patients, so more targets are being investigated. VISTA (V-domain Ig suppressor of T cell activation) is a novel immune checkpoint that is broadly expressed within hematopoietic cells and multiple cancers (low expressing frequency on solid tumors), particularly those with a poor immunotherapy response rate. As a result, VISTA has been identified as an appealing target for immunotherapy, and several VISTA inhibitors are currently in clinical and preclinical trials. In this review, the structural features and binding partners of VISTA are summarized, and we describe the latest developments of monoclonal antibodies and small molecules targeting VISTA as well as possible future directions for development of therapies targeting VISTA.
阻断细胞毒性 T 淋巴细胞相关抗原 4（CTLA-4）和程序性细胞死亡蛋白 1/程序性细胞死亡配体 1（PD-1/PD-L1）已产生显著的治疗效果，但仅在一部分患者中有效，因此正在研究更多的靶点。VISTA（T 细胞激活的 V 域免疫球蛋白抑制剂）是一种新型免疫检查点，广泛表达于造血细胞和多种癌症（实体瘤中表达频率较低），特别是免疫治疗反应率低的癌症。因此，VISTA 已被确定为免疫治疗的一个有吸引力的靶点，目前有几种 VISTA 抑制剂正在进行临床前和临床试验。在这篇综述中，总结了 VISTA 的结构特征和结合伙伴，描述了针对 VISTA 的单克隆抗体和小分子的最新进展，以及针对 VISTA 的治疗方法的可能发展方向。
