PDF(Pubmed)
Abstract：
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.
摘要：
免疫检查点抑制剂的应用已被证明是癌症的有效治疗方法。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），淋巴细胞活化基因-3(LAG-3)受到了广泛的关注,并且已经在许多肿瘤中评估了针对这些检查点的抗体或抑制剂（单独或组合）的功效。本文简要概述了PD-1和LAG-3检查点，然后将重点转移到体内和体外实验中PD-1和LAG-3抗体的联合使用。在体外实验中，我们检查了这些抑制剂在T细胞上的表达和激活之间的相关性，并在准备体内实验时评估动物的毒性。然后在黑色素瘤动物模型中总结PD-1和LAG-3抗体联合使用的效果，MC38癌，和其他肿瘤。在临床研究中,在黑色素瘤患者中评估了这些抗体的联合应用，结直肠,乳房,和肾细胞癌，以及其他实体瘤。总的来说,PD-1和LAG-3抗体的组合在体内和体外研究中都显示出有希望的结果.
