Fig. 2: MCLA-145 binds with high affinity and to a unique epitope on CD137.

a Summary of SPR and cell-based affinity measurements for binding to PD-L1; b Summary of SPR and cell-based affinity measurements for binding to CD137; c SPR affinity analysis showing dual binding of human PD-L1 and CD137 to immobilized MCLA-145. Green curves: human PD-L1 injected first followed by injection of human CD137 or running buffer. Red curves: human CD137 injected followed by human PD-L1 or running buffer; d surface homology model of the CD137 ectodomain in complex with CD137L (PDB: 6MGP), the CRD domains 1–4 are shaded in yellow, green, purple and cyan respectively, CD137L is depicted as a gray ribbon, the backbone and residues of urelumab* (dark red) and utomilumab* (orange) epitopes are highlighted, critical binding residues for MCLA-145 as determined by alanine scanning are shown as solid blue spheres; e binding of labeled CD137L to CHO-CD137⁺ cells was measured by flow analysis in a titration series of MCLA-145 and control antibodies f NFAT activity of PD-1 reporter cells cocultured with CHO-PD-L1⁺ and incubated with a titration of MCLA-145 and control antibodies.