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The Extra domain B (ED-B) of human fibronectin is a 91-amino acid type III repeat generated through alternative splicing of the fibronectin pre-mRNA [Mol Oncol. 2020 Jul;14(7):1555-1568]. While virtually absent in healthy adult tissues, ED-B is highly expressed during periods of intense tissue remodeling, such as embryogenesis and wound healing, and is a prominent marker of pathological angiogenesis in the tumor microenvironment [Mol Oncol. 2020; Expert Opin Ther Targets. 2005;9(3):491-500]. It is deposited by cancer-associated fibroblasts and endothelial cells in the neovasculature of nearly all solid tumors, making it a highly specific oncofetal antigen [Mol Oncol. 2020; Mol Cancer Ther. 2022;21(9):1462-72]. Due to its high tumor-to-normal tissue ratio and accessibility within the extracellular matrix, ED-B is a premier target for the delivery of therapeutic payloads, including cytokines, radionuclides, and cytotoxic drugs [Mol Oncol. 2020; BMJ Phase 1 Study, 2023]. Clinical strategies, such as the L19 antibody fragment, leverage this specificity to concentrate potent agents at the tumor site, enhancing the therapeutic index and minimizing systemic side effects [Mol Oncol. 2020; Expert Opin Ther Targets. 2005]. Beyond oncology, ED-B is also investigated as a biomarker and therapeutic target in fibrotic and inflammatory conditions [AlzDiscovery.org, 2024].
Targeted delivery of therapeutic payloads (cytokines, radionuclides, or cytotoxic drugs) to the tumor microenvironment and neovasculature by binding specifically to the ED-B domain; disruption of extracellular matrix integrity and inhibition of angiogenesis [Mol Oncol. 2020; Mol Cancer Ther. 2022].
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