Lee Jii Bum, Ha Sang-Jun, Kim Hye Ryun
Division of Hemato-oncology, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, South Korea.
Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea.
Front Pharmacol. 2021 May 6;12:681320. doi: 10.3389/fphar.2021.681320. eCollection 2021.
The success of immune checkpoint inhibitors (ICIs), notably anti-cytotoxic T lymphocyte associated antigen-4 (CTLA-4) as well as inhibitors of CTLA-4, programmed death 1 (PD-1), and programmed death ligand-1 (PD-L1), has revolutionized treatment options for solid tumors. However, the lack of response to treatment, in terms of or acquired resistance, and immune related adverse events (IRAE) remain as hurdles. One mechanisms to overcome the limitations of ICIs is to target other immune checkpoints associated with tumor microenvironment. Immune checkpoints such as lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin and ITIM domain (TIGIT), T cell immunoglobulin and mucin-domain containing-3 (TIM-3), V-domain immunoglobulin suppressor of T cell activation (VISTA), B7 homolog 3 protein (B7-H3), inducible T cell costimulatory (ICOS), and B and T lymphocyte attenuator (BTLA) are feasible and promising options for treating solid tumors, and clinical trials are currently under active investigation. This review aims to summarize the clinical aspects of the immune checkpoints and introduce novel agents targeting these checkpoints.
免疫检查点抑制剂(ICI)的成功,尤其是抗细胞毒性T淋巴细胞相关抗原4(CTLA-4)以及CTLA-4、程序性死亡1(PD-1)和程序性死亡配体1(PD-L1)的抑制剂,彻底改变了实体瘤的治疗选择。然而,在疗效或获得性耐药方面缺乏反应以及免疫相关不良事件(IRAE)仍然是障碍。克服ICI局限性的一种机制是靶向与肿瘤微环境相关的其他免疫检查点。淋巴细胞激活基因3(LAG-3)、T细胞免疫球蛋白和ITIM结构域(TIGIT)、含T细胞免疫球蛋白和粘蛋白结构域3(TIM-3)、T细胞激活的V结构域免疫球蛋白抑制剂(VISTA)、B7同源物3蛋白(B7-H3)、诱导性T细胞共刺激分子(ICOS)以及B和T淋巴细胞衰减器(BTLA)等免疫检查点是治疗实体瘤可行且有前景的选择,目前正在积极开展相关临床试验。本综述旨在总结免疫检查点的临床情况,并介绍靶向这些检查点的新型药物。