Abstract：
In recent years, several monoclonal antibodies (mAbs) targeting PD-L1 have been licensed by the FDA for use in the treatment of cancer, demonstrating the effectiveness of blocking immune checkpoints, particularly the PD-1/PD-L1 pathway. Although mAb-based therapies have made great strides, they still have their limitations, and new small-molecule or PROTAC-molecule inhibitors that can block the PD-1/PD-L1 axis are desperately needed. Therefore, it is crucial to translate initial in vitro discoveries into appropriate in vivo animal models when creating PD-L1-blocking therapies. Due to their widespread availability and low experimental expenses, classical immunocompetent mice are appealing for research purposes. However, it is yet unclear whether the mouse (m) PD-L1 interaction with human (h) PD-1 in vivo would produce a functional immunological checkpoint. In this review, we summarize the in vitro and in vivo experimental studies of small molecules and PROTAC molecules, particularly the distinctions between mPD-L1 as a target and hPD-L1 as a target.
摘要：
近年来,几种靶向PD-L1的单克隆抗体（mAb）已被FDA批准用于治疗癌症，证明了阻断免疫检查点的有效性，特别是PD-1/PD-L1途径。尽管基于mAb的疗法取得了长足的进步，他们仍然有自己的局限性，迫切需要能够阻断PD-1/PD-L1轴的新的小分子或PROTAC分子抑制剂。因此,在创建PD-L1阻断疗法时,将最初的体外发现转化为合适的体内动物模型至关重要.由于其广泛的可用性和较低的实验费用，经典的免疫活性小鼠对研究目的很有吸引力。然而,目前尚不清楚小鼠(m)PD-L1与人(h)PD-1的体内相互作用是否会产生功能性免疫检查点.在这次审查中,我们总结了小分子和PROTAC分子的体外和体内实验研究，特别是mPD-L1作为靶标和hPD-L1作为靶标之间的区别。
