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The extra domain B (EDB) of fibronectin, also known as EIIIB, is a 91-amino acid type III homology domain that is incorporated into the fibronectin protein through alternative splicing of the pre-mRNA (UniProt P02751). Under normal physiological conditions in adults, EDB is virtually undetectable; however, it is highly expressed during embryonic development and in pathological states involving active angiogenesis and tissue remodeling (PubMed: 22403338). This restricted expression pattern makes EDB a prominent marker of neovasculature in various solid tumors, including glioblastoma, lung cancer, and colorectal cancer (PubMed: 10449144). In the tumor microenvironment, EDB-containing fibronectin facilitates cell adhesion and migration, contributing to tumor progression and metastasis (PubMed: 16401712). Because of its high stability and accessibility in the extracellular matrix, EDB has become a primary target for the development of antibody-based therapeutics and diagnostics (PubMed: 18413681). Most clinical-stage agents targeting EDB, such as Darleukin and Fibromun, utilize the L19 antibody fragment to deliver payloads like interleukin-2 or tumor necrosis factor directly to the tumor site to stimulate a localized immune response (Philogen Pipeline).
Targeted delivery of therapeutic payloads such as cytokines, radionuclides, or cytotoxic drugs to the tumor microenvironment and neovasculature by binding to the EDB domain of fibronectin.
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