Target intelligence / Profile preview

Oncofetal fibronectin (Extra Domain B) (onfFN (ED-B))

Target
onfFN (ED-B)
Molecular classification
Extracellular matrix protein, Glycoprotein, Splice variant
01

Overview

Oncofetal fibronectin, specifically the Extra Domain B (ED-B) variant, is a splice isoform of fibronectin that is virtually absent in normal adult tissues but highly expressed during embryogenesis and in the stroma of aggressive tumors, including melanoma. This variant is generated through alternative splicing of the fibronectin pre-mRNA and is closely associated with tumor angiogenesis and the epithelial-to-mesenchymal transition (EMT) required for metastasis. In melanoma, ED-B fibronectin serves as a specific marker for the tumor neovasculature and the invasive front of the tumor, facilitating cell migration and survival. Because of its high tumor-specificity and accessibility within the extracellular matrix, it has become a primary target for antibody-based delivery of therapeutic agents. Drugs like L19-IL2 and L19-TNF utilize high-affinity antibodies to concentrate potent cytokines directly at the tumor site, enhancing the anti-tumor immune response while minimizing systemic toxicity.

Other names
ED-B fibronectinB-fibronectinOncofetal fibronectinExtra Domain B-containing fibronectinEDB-FNEIIIB-containing fibronectin
02

Mechanism of action

Targeted delivery of immunomodulatory cytokines (e.g., IL-2, TNF) or pro-coagulant factors to the tumor microenvironment by binding to the ED-B domain of fibronectin, which is specifically expressed in neovascular structures and tumor stroma.

03

Biological functions

Cell adhesionCell migrationAngiogenesisExtracellular matrix assemblyTissue remodeling
04

Disease associations

MelanomaCancer metastasisTumor angiogenesisSolid tumors
05

Safety considerations

Infusion-related reactionsCytokine release syndrome (when conjugated to IL-2 or TNF)Potential for off-target effects in wound healing areas where ED-B may be transiently expressed
06

Interacting drugs

L19-IL2 (Darleukin)

4 more in the full profile.

07

Biomarkers

ED-B fibronectin expression (detected by IHC or PET imaging with L19)FDC-6 immunoreactivity

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