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DT390-BiscFv806 is a **bivalent recombinant immunotoxin** designed for targeted cancer therapy. It consists of the **catalytic and translocation domains of diphtheria toxin (DT390)** fused to two single-chain variable fragments (scFv) derived from the humanized monoclonal antibody **mAb806**, which specifically recognizes both **epidermal growth factor receptor (EGFR)** and its mutant form **EGFRvIII**. EGFR and EGFRvIII are overexpressed in multiple cancers, including glioblastoma multiforme (GBM), head and neck squamous cell carcinoma (HNSCC), lung, breast, prostate, and ovarian cancers. DT390-BiscFv806 exhibits potent and selective cytotoxicity toward cancer cells expressing EGFR and/or EGFRvIII, with much greater activity against cells expressing the mutant EGFRvIII. Its mechanism involves internalization into target cells, where the toxin fragment inhibits protein synthesis, leading to tumor cell death. The immunotoxin shows promising **antitumor activity in vitro** and **in vivo** xenograft models, with a favorable specificity profile due to minimal binding to EGFR in normal tissues[1][3][5][6].
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