在过去的二十年中，免疫疗法越来越被认为是大多数癌症的一线治疗方法。其中一种治疗方法是免疫检查点阻断（ICB），它在临床试验中针对各种实体瘤显示出有希望的结果。单克隆抗体 (mAb) 目前可用作免疫检查点抑制剂 (ICIs)。这些 ICI 针对特定的免疫检查点，包括细胞毒性 T 淋巴细胞相关抗原 4 (CTLA-4) 和程序性细胞死亡蛋白 1 (PD-1)。临床试验结果有力地支持了这种免疫治疗方法的可行性。然而，由于肿瘤免疫逃避机制抵消了宿主免疫反应，相当一部分癌症患者对治疗产生了耐药性或耐受性。因此，大量研究重点旨在确定其他 ICI 或协同抑制受体，以增强抗 PD-1、抗程序性细胞死亡配体 1（抗 PD-L1）和抗 CTLA-4 治疗的有效性。最近，一些免疫检查点分子靶点已被确定，如具有Ig和ITIM结构域的T细胞免疫受体（TIGIT）、含粘蛋白结构域3（TIM-3）、淋巴细胞激活基因3（LAG-3）、V结构域T 细胞激活免疫球蛋白抑制因子 (VISTA)、B 和 T 淋巴细胞衰减因子 (BTLA) 和信号调节蛋白 α (SIRPα)。针对这些分子的功能性单克隆抗体正在开发中。 CTLA-4、PD-1/PD-L1 和其他最近发现的具有独特结构的免疫检查点蛋白处于研究的前沿。本综述讨论了这些结构，以及针对这些免疫检查点分子的 mAb 的临床进展及其潜在应用。版权所有：© 2024，作者。

Over the past two decades, immunotherapies have increasingly been considered as first-line treatments for most cancers. One such treatment is immune checkpoint blockade (ICB), which has demonstrated promising results against various solid tumors in clinical trials. Monoclonal antibodies (mAbs) are currently available as immune checkpoint inhibitors (ICIs). These ICIs target specific immune checkpoints, including cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1). Clinical trial results strongly support the feasibility of this immunotherapeutic approach. However, a substantial proportion of patients with cancer develop resistance or tolerance to treatment, owing to tumor immune evasion mechanisms that counteract the host immune response. Consequently, substantial research focus has been aimed at identifying additional ICIs or synergistic inhibitory receptors to enhance the effectiveness of anti-PD-1, anti-programmed cell death ligand 1 (anti-PD-L1), and anti-CTLA-4 treatments. Recently, several immune checkpoint molecular targets have been identified, such as T cell immunoreceptor with Ig and ITIM domains (TIGIT), mucin domain containing-3 (TIM-3), lymphocyte activation gene-3 (LAG-3), V-domain immunoglobulin suppressor of T cell activation (VISTA), B and T lymphocyte attenuator (BTLA), and signal-regulatory protein α (SIRPα). Functional mAbs targeting these molecules are under development. CTLA-4, PD-1/PD-L1, and other recently discovered immune checkpoint proteins with distinct structures are at the forefront of research. This review discusses these structures, as well as clinical progress in mAbs targeting these immune checkpoint molecules and their potential applications.Copyright: © 2024, The Authors.