计程死亡配体1（PD-(L)1）、细胞性T淋巴细胞相关蛋白4（CTLA-4）和淋巴细胞活化基因3（LAG-3）抑制剂是癌症治疗的最新突破，但并非所有患者都受益。因此，正在研究新的疗法，如抗-TIGIT [抗T细胞免疫受体和免疫球蛋白（Ig）和免疫受体酪氨酸基底抑制性结构域] 抗体。TIGIT 是通过多种机制抑制淋巴细胞 T 细胞的免疫检查点。体外模型显示，它的抑制可以恢复抗肿瘤反应。此外，它与抗-PD-(L)1 疗法的关联可能会协同改善存活率。我们对在 PubMed 数据库中引用 TIGIT 的临床试验进行了评估，发现三项关于抗-TIGIT 疗法的临床试验已发表。Vibostolimab 在 I 期中独立或与Pembrolizumab 联用进行了评估。组合疗法对于非小细胞肺癌（NSCLC）中 PD-1 未经抗性的患者的客观反应率为 26%。Etigilimab 在 I 期中单独或与 nivolumab 联用进行了测试，但由于营业原因该研究被停止了。在 II 期 CITYSCAPE 试验中，Tiragolumab 在与 Atezolizumab 的联用中表现出更高的客观反应率和无进展生存期，在 PD-L1 高度进展的 NSCLC 患者中比单独使用 Atezolizumab 更有效。ClinicalTrials.gov 数据库中有 70 项针对癌症患者的抗-TIGIT 试验，其中 47 项正在招募中。只有七项是 III 期的，其中五项是针对 NSCLC 患者的，大多采用联合治疗。来自 I-II 期的试验数据突出显示，针对 TIGIT 表示出一种安全的治疗方法，在添加抗-PD-(L)1 抗体时，毒性剖面维持在可接受的范围内。常见的不良事件包括瘙痒、皮疹和疲劳。三分之一的患者报告了 3-4 级的不良事件。抗-TIGIT 抗体正在作为一种新的免疫治疗方法进行开发。一个有前途的研究领域包括与 PD-1 抗体联合治疗晚期 NSCLC。版权©2023年作者。由Elsevier Ltd.出版。保留所有权利。

Programmed death-ligand 1[PD-(L)1], cytotoxic T-lymphocyte associated protein 4 (CTLA-4), and lymphocyte-activation gene 3 (LAG-3) inhibitors are recent breakthroughs in cancer treatment, however not all patients benefit from it. Thus new therapies are under investigation, such as anti-TIGIT [anti-T-cell immunoreceptor with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory motif domains] antibodies. TIGIT is an immune checkpoint inhibiting lymphocyte T cells by several mechanisms. In vitro models showed its inhibition could restore antitumor response. Furthermore, its association with anti-PD-(L)1 therapies could synergistically improve survival. We carried out a review of the clinical trial about TIGIT referenced in the PubMed database, finding three published clinical trials on anti-TIGIT therapies. Vibostolimab was evaluated in a phase I alone or in combination with pembrolizumab. The combination had an objective response rate of 26% in patients with a non-small-cell lung cancer (NSCLC) naïve of anti-programmed cell death protein 1 (anti-PD-1). Etigilimab was tested in a phase I alone or in combination with nivolumab, but the study was stopped due to business reasons. In the phase II CITYSCAPE trial, tiragolumab demonstrated higher objective response rate and progression-free survival in combination with atezolizumab than atezolizumab alone in advanced PD-L1-high NSCLC. The ClinicalTrials.gov database references 70 trials of anti-TIGIT in patients with cancer, 47 of them with ongoing recruitment. Only seven were phase III, including five about patients with NSCLC, mostly with combination therapy. Data from phase I-II trials highlighted that targeting TIGIT represents a safe therapeutic approach, with an acceptable toxicity profile maintained when adding anti-PD-(L)1 antibodies. Frequent adverse events were pruritus, rash, and fatigue. Grade 3-4 adverse events were reported in nearly one in three patients. Anti-TIGIT antibodies are under development as a novel immunotherapy approach. A promising research area includes the combination with anti-PD-1 therapies in advanced NSCLCs.Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.