Extra Domain B of fibronectin (ED-B) (ED-B)

The Extra Domain B (ED-B) of fibronectin is a 91-amino acid type III homology domain that is specifically incorporated into the fibronectin molecule through alternative splicing of the pre-mRNA during periods of active tissue remodeling [1: UniProt P02751]. While virtually absent in healthy adult tissues, the ED-B domain is highly expressed in the neovasculature and extracellular matrix of most aggressive solid tumors, as well as in inflammatory conditions like rheumatoid arthritis [2: PubMed PMID 16138053]. This stark difference in expression makes ED-B a premier target for the selective delivery of therapeutic agents, a strategy known as vascular targeting [3: PubMed PMID 19145619]. L19TNF (also known as Fibromun) is a clinical-stage immunocytokine consisting of the L19 antibody fragment, which binds the ED-B domain with picomolar affinity, fused to human tumor necrosis factor-alpha (TNF) [4: Philogen Pipeline]. By binding to ED-B, L19TNF concentrates TNF at the tumor site, where it induces hemorrhagic necrosis of the tumor vessels and stimulates a localized immune response [5: PubMed PMID 25913175]. This targeted approach significantly enhances the therapeutic window of TNF, allowing for potent anti-tumor activity while mitigating the severe systemic side effects typically associated with cytokine therapy [6: PubMed PMID 23633449]. Clinical trials have explored L19TNF in combination with other agents for the treatment of soft tissue sarcoma and melanoma, demonstrating its potential to alter the tumor microenvironment and improve patient outcomes [7: ClinicalTrials.gov].

Other names

EDB-FNED-B fibronectinOncofetal fibronectinB-FNExtra type III domain B of fibronectin

Targeted delivery of effector molecules (cytokines or radionuclides) to the tumor microenvironment and neovasculature through high-affinity binding to the ED-B domain, leading to localized immune activation or direct cytotoxicity.