Pharmacotherapeutics Unit, Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.
Pharmacotherapeutics Unit, Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.
Pharmacol Ther. 2021 Nov;227:107870. doi: 10.1016/j.pharmthera.2021.107870. Epub 2021 Apr 22.
Cancer immunotherapy is an option to enhance physiological defence mechanism to fight cancer, where natural substances (e.g., antigen/antibody) or small synthetic molecule can be utilized to improve and restore the immune system to stop or slacken the development of malignant cells, stop metastasis and/or help the immune response with synthetic monoclonal antibodies (mAbs) and tumour-agnostic therapy to eliminate cancer cells. Interaction between the programmed cell death ligand 1 (PD-L1) and its receptor (programmed cell death protein 1, PD-1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) linked signalling pathways have been identified as perilous towards the body's immune mechanism in regulating the progression of cancer. It is known that certain cancers use these pathways to evade the body's defence mechanism. The immune system is capable of responding to cancer by stalling these trails with specific synthetic antibodies or immune checkpoint inhibitors, which can ultimately either stop or slow cancer cell development. Recent findings and data suggested that using such inhibitors invigorated a new approach to cancer treatment. These inhibitors usually activate the immune system to identify and eliminate cancer cells rather than attacking tumour cells directly. PD-1/PD-L1 inhibitors have already been substantiated for their efficacy in over twenty variations of cancer through different clinical trials. Studies on molecular interaction with existing PD-1/PD-L1 inhibitors that are mainly dominated by antibodies are constantly generating new ideas to develop novel inhibitors. This review has summarised information on reported and/or patented small molecules and peptides for their ability to interact with the PD-1/PD-L1 as a potential anticancer strategy.
癌症免疫疗法是一种增强生理防御机制以对抗癌症的方法，其中可以利用天然物质（例如抗原/抗体）或小分子合成物来改善和恢复免疫系统，以阻止或减缓恶性细胞的发展、阻止转移和/或利用合成单克隆抗体（mAbs）和肿瘤不可知疗法来帮助免疫反应消除癌细胞。程序性细胞死亡配体 1（PD-L1）与其受体（程序性死亡蛋白 1，PD-1）以及细胞毒性 T 淋巴细胞相关蛋白 4（CTLA4）之间的相互作用信号通路已被确定为身体免疫机制调节癌症进展的危险途径。已知某些癌症利用这些途径逃避身体的防御机制。免疫系统能够通过用特定的合成抗体或免疫检查点抑制剂阻止这些途径来对癌症做出反应，这些抑制剂最终可以阻止或减缓癌细胞的发展。最近的研究结果和数据表明，使用这些抑制剂为癌症治疗提供了一种新方法。这些抑制剂通常激活免疫系统来识别和消除癌细胞，而不是直接攻击肿瘤细胞。已经通过不同的临床试验证实了 PD-1/PD-L1 抑制剂在二十多种癌症中的疗效。关于现有 PD-1/PD-L1 抑制剂的分子相互作用的研究主要由抗体主导，不断产生开发新型抑制剂的新想法。这篇综述总结了有关报道的和/或已获得专利的小分子和肽与 PD-1/PD-L1 相互作用的信息，作为一种潜在的抗癌策略。
