Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 21, Pages -Publisher
MDPI
DOI: 10.3390/ijms222111797
Keywords
PD-L1 inhibitor; immune checkpoint blockade; immunotherapy
Funding
- National Science Centre, Poland [UMO-2020/39/D/ST4/01344]
- Foundation for Polish Science
- Priority Research Area SciMat
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This article compares representative molecules from different classes in terms of their PD-1/PD-L1 dissociation capacity and in vitro bioactivity. Recent discoveries underscore important differences in the mechanisms of action of these molecules, with one principal feature to consider being the eventual human PD-L1 specificity.
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.
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