Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126, Pisa, Italy.
Mini Rev Med Chem. 2022;22(14):1816-1827. doi: 10.2174/1389557522666220217110925.
In 2018, James Allison and Tasuku Honjo received the Nobel Prize in physiology or medicine to discover tumor therapy by inhibition of negative immune regulation. Immunotherapy stimulates T-cells to fight cancer cells by blocking different immune checkpoint pathways. The interaction between programmed cell death 1 (PD-1) and its ligand PD-L1 (Programmed cell death ligand 1) is one of the main pathways. Of note, interfering with this pathway is already exploited in clinical cancer therapy, demonstrating that it is one of the key factors involved in the immune escape mechanism of cancer. The development of monoclonal antibodies (mAbs) that possess the ability to inhibit the interactions between PD-1/PD-L1 has radically made the difference in cancer immunotherapy. Yet, due to the many drawbacks of this therapy, the research shifted its efforts towards the development of novel small molecules. This may constitute hope and an arduous challenge in fighting cancer. This paper reviews the recent primary literature concerning the development of novel small molecules able to block the interaction between PD-1 and its ligand PD-L1.
2018 年，詹姆斯·艾利森（James Allison）和本庶佑（Tasuku Honjo）因发现抑制负免疫调节的肿瘤疗法而获得诺贝尔生理学或医学奖。免疫疗法通过阻断不同的免疫检查点途径来刺激 T 细胞对抗癌细胞。程序性细胞死亡蛋白 1（PD-1）与其配体 PD-L1（程序性死亡配体 1）之间的相互作用是主要途径之一。值得注意的是，干扰这条途径已被用于临床癌症治疗，表明它是癌症免疫逃逸机制中涉及的关键因素之一。具有抑制 PD-1/PD-L1 相互作用能力的单克隆抗体（mAbs）的开发在癌症免疫治疗中带来了根本性的改变。然而，由于这种疗法存在许多缺点，研究已将其努力转向开发新型小分子。这可能是抗击癌症的希望和艰巨挑战。本文综述了近期关于能够阻断 PD-1 与其配体 PD-L1 相互作用的新型小分子的发展的主要文献。
