School of Clinical Medicine, Shandong Second Medical University, Weifang, China.
Linyi People's Hospital, Linyi, China.
Biomol Biomed. 2024 Apr 6;24(4):764-774. doi: 10.17305/bb.2024.10339.
The application of immune checkpoint inhibitors has proven to be an effective treatment for cancer. Immune checkpoints such as programmed cell death protein 1/programmed cell death protein 1 ligand 1 (PD-1/PD-L1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), T-cell immunoglobulin-3 (TIM-3), T-cell immunoglobulin and ITIM domain (TIGIT), and lymphocyte activation gene-3 (LAG-3) have received extensive attention, and the efficacy of antibodies or inhibitors against these checkpoints (either alone or in combination) has been evaluated in many tumors. This paper provides a brief overview of the PD-1 and LAG-3 checkpoints, and then shifts focus to the combined use of PD-1 and LAG-3 antibodies in both in vivo and in vitro experiments. In the in vitro experiments, we examined the correlation between the expression and activation of these inhibitors on T cells, and also assessed toxicity in animals in preparation for in vivo experiments. The effects of the combined use of PD-1 and LAG-3 antibodies were then summarized in animal models of melanoma, MC38 carcinoma, and other tumors. In clinical studies, the combined application of these antibodies was assessed in patients with melanoma, colorectal, breast, and renal cell cancers, as well as other solid tumors. In general, the combination of PD-1 and LAG-3 antibodies has shown promising results in both in vivo and in vitro studies.
免疫检查点抑制剂的应用已被证明是癌症治疗的有效手段。免疫检查点如程序性细胞死亡蛋白 1/程序性细胞死亡蛋白 1 配体 1(PD-1/PD-L1)、细胞毒性 T 淋巴细胞相关蛋白 4(CTLA-4)、T 细胞免疫球蛋白-3(TIM-3)、T 细胞免疫球蛋白和 ITIM 结构域(TIGIT)和淋巴细胞激活基因-3(LAG-3)受到广泛关注,针对这些检查点的抗体或抑制剂(单独或联合使用)在许多肿瘤中的疗效已得到评估。本文简要概述了 PD-1 和 LAG-3 检查点,然后将重点转移到 PD-1 和 LAG-3 抗体在体内和体外实验中的联合使用上。在体外实验中,我们研究了 T 细胞上这些抑制剂的表达和激活之间的相关性,并评估了动物实验中的毒性,为体内实验做准备。然后在黑色素瘤、MC38 癌等肿瘤的动物模型中总结了 PD-1 和 LAG-3 抗体联合使用的效果。在临床研究中,评估了这些抗体在黑色素瘤、结直肠癌、乳腺癌和肾细胞癌以及其他实体瘤患者中的联合应用。总的来说,PD-1 和 LAG-3 抗体的联合应用在体内和体外研究中均显示出良好的效果。