Figure 2.

MGD019 Molecular Structure and Bispecific Binding to PD-1 and CTLA-4

(A) MGD019 is a tetravalent bispecific (2 × 2) Fc-bearing DART molecule.

(B) Binding of MGD019 (red diamonds), parental PD-1 mAb retifanlimab (blue squares), parental CTLA-4 mAb 4B6 (green triangles), or isotype control (black circles) to Jurkat/PD-1 cells and blockade of PD-L1 binding to the cells.

(C) Binding to Jurkat/CTLA-4 cells and blockade of B7-1 binding to the cells.

(D) Re-activation of β-galactosidase (β-gal) upon co-engagement of PD-1 and CTLA-4 by MGD019 in PathHunter PD-1⁺CTLA-4⁺ assay. Error bars depict standard errors of the mean (SEMs).

(E) Binding to in vitro-stimulated, PD-1⁺/CTLA-4⁺ primary T cells and blockade of B7.1 binding to Jurkat PD-1⁺/CTLA-4⁺ cells.

(F) Blockade B7.1 binding to Jurkat PD-1⁺/CTLA-4⁺ by MGD019 or CTLA-4 mAbs alone or in the presence of a 10× concentration of competing PD-1 mAbs (open red diamonds and purple crosses, respectively).

(G) Interaction of MGD019 with single- and dual-expressing cells. Average (EC₅₀) values of PD-1 (blue) and CTLA-4 (yellow) ligand binding blockade (Table S1). Representative experiments out of ≥3 independent repeats are shown in (B)–(F).

See also Table S1 and Figures S2 and S3.