Fibronectin extradomain B (ED-B)

Fibronectin extradomain B (ED-B) is an alternatively spliced isoform of the extracellular matrix glycoprotein fibronectin, often referred to as an oncofetal antigen due to its high expression during embryogenesis and near-total absence in healthy adult tissues [1, 4, 9]. It is specifically upregulated in the stroma and neovasculature of a wide range of solid tumors, where it plays a critical role in promoting angiogenesis, cell adhesion, and tissue remodeling [3, 8, 13]. Because of its high specificity for the tumor microenvironment and its accessibility as an extracellular matrix component, ED-B serves as an ideal target for the delivery of therapeutic agents [1, 7, 14]. Therapeutic strategies targeting ED-B include antibody-cytokine fusions, such as L19-IL2 and L19-TNF, which aim to concentrate immune-stimulating molecules at the tumor site, as well as antibody-drug conjugates and radiopharmaceuticals [4, 13, 15]. These approaches leverage the stable anchor provided by ED-B in the tumor stroma to achieve high local concentrations of treatment while minimizing systemic toxicity [1, 17]. In addition to cancer, ED-B expression is observed in other conditions involving pathological neovascularization, such as atherosclerosis and certain inflammatory diseases [12, 14]. The most well-characterized targeting moiety is the L19 antibody, which has been extensively used in clinical trials to deliver cytokines like IL-2 and TNF-alpha directly to the tumor site [4, 13].

Other names

EDBED-BEIIIBOncofetal fibronectinExtra domain B of fibronectin

Targeted delivery of therapeutic payloads (such as cytokines, radioisotopes, or cytotoxic drugs) to the tumor microenvironment and neovasculature by binding to the extradomain B of fibronectin in the extracellular matrix [1, 4, 13].