Portal de Periódicos da CAPES

PD-L1 Inhibitors: Different Classes, Activities, and Mechanisms of Action

2021; Multidisciplinary Digital Publishing Institute; Volume: 22; Issue: 21 Linguagem: Inglês

10.3390/ijms222111797

1661-6596

Ewa Surmiak, Katarzyna Magiera‐Mularz, Bogdan Musielak, Damian Muszak, Justyna Kocik, Radosław Kitel, Jacek Plewka, Tad A. Holak, Łukasz Skalniak,

Immunotherapy and Immune Responses

Targeting the programmed cell death protein 1/programmed cell death 1 ligand 1 (PD-1/PD-L1) interaction has become an established strategy for cancer immunotherapy. Although hundreds of small-molecule, peptide, and peptidomimetic inhibitors have been proposed in recent years, only a limited number of drug candidates show good PD-1/PD-L1 blocking activity in cell-based assays. In this article, we compare representative molecules from different classes in terms of their PD-1/PD-L1 dissociation capacity measured by HTRF and in vitro bioactivity determined by the immune checkpoint blockade (ICB) co-culture assay. We point to recent discoveries that underscore important differences in the mechanisms of action of these molecules and also indicate one principal feature that needs to be considered, which is the eventual human PD-L1 specificity.