Imaging and quantifying analysis the binding behavior of PD-L1 at molecular resolution by atomic force microscopy

Novel perspective for protein–drug interaction analysis: atomic force microscope

“…8C). Interestingly, similar unbinding force values of PD-L1 with anti-PD-L1 were obtained on the model as well as on the cell surface, 77 which indicates the reliability of the obtained data from the surface model. Recently, Kim et al developed a universal immobilization method to measure the interaction between mAbs and cell-surface targets 115 (Fig.…”

“…76 Qin et al investigated the interaction of programmed cell death ligand-1 (PD-L1) with its antibody and programmed cell death protein-1 (PD-1), and the results showed that the difference in the energy barrier Δ(Δ E ) between PD-L1/anti-PD-L1 antibody and PD-L1/PD-1 was −0.632 k B T (ref. 77) (Fig. 6C).…”

Photo-induced crosslinked and anti-PD-L1 peptide incorporated liposomes to promote PD-L1 multivalent binding for effective immune checkpoint blockade therapy

“…In case of PD-L1 mAb-treated mGFP-CT26 cells, mGFP-labeled PD-L1 (green color) on the cell surface was significantly decreased until 6 h of incubation, but that was rapidly regenerated from 9 h post-incubation. These results indicate that PD-L1 mAb-induced PD-L1 blockade results in PD-L1 recycling owing to rapid dissociation of PD-L1 mAbs from PD-L1 and its subcellular fate that enters into the recycling endosomes 9 , 24 , 25 . In contrast, ICB-LPs +UV induced durable PD-L1 degradation in the mGFP-CT26 cells; approximately 90% of PD-L1 disappeared in the tumor cells, whereas over 80% of PD-L1 was regenerated after 24 h of PD-L1 mAb treatment ( Fig.…”

“…However, those complexes were rapidly dissociated after 6 h of incubation, and only a small amount of PD-L1 mAbs was observed in the mGFP-CT26 cells at 12 h post-incubation. This is because the PD-L1/PD-L1 mAb complexes collapse more easily than PD-L1/PD-1 axis 24 ; in addition, the dissociation rates of those complexes are highly accelerated in the acidic endosomes 25 . Therefore, these results show that the PD-L1 mAbs are mostly dissociated from PD-L1 in the cells within 12 h of incubation.…”

All-in-one glycol chitosan nanoparticles for co-delivery of doxorubicin and anti-PD-L1 peptide in cancer immunotherapy

“…Importantly, the PD-L1 Ab/PD-L1 complexes were rapidly dissociated at 12 h post-incubation because they collapse more easily than the PD-L1/PD-1 axis [ 45 ]. This is also attributable to that the dissociation rate of PD-L1 Ab from PD-L1 is significantly accelerated in the acidic endosome [ 46 ]. In addition, PD-L1 Abs on the cell surface or cytoplasm were greatly reduced due to the extensive lysosomal degradation, thus PD-L1 regeneration was clearly observed on the cell membrane after 12 h of incubation.…”