Fig. 3.

Mechanism of action of bintrafusp alfa, a first‐in‐class bifunctional fusion protein composed of the extracellular domain of TGF‐βRII to function as a TGF‐β ‘trap’ fused to a human IgG1 antibody blocking PD‐L1. Through colocalized, simultaneous inhibition of these pathways, bintrafusp alfa has the potential to enhance immune cell access to the tumor, limit metastasis, and improve response to anticancer therapy. Bintrafusp alfa has the potential to inhibit angiogenesis through suppression of TGF‐β activity via stromal modulation and may restore normal vascular homeostasis, thereby enhancing drug delivery and T‐cell infiltration into the TME. CAF, cancer‐associated fibroblast; EMT, epithelial–mesenchymal transition; NK, natural killer; PD‐1, programmed death 1; PD‐L1, programmed death ligand 1; TAM, tumor‐associated macrophage; TGF, transforming growth factor; TME, tumor microenvironment.