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TrkB-targeting DVD-ADC is an antibody-drug conjugate (ADC) specifically engineered for targeted cancer therapy, notably in triple-negative breast cancer. It utilizes a *dual variable domain* (DVD) antibody format that combines the variable domains of an anti-TrkB antibody (targeting tropomyosin receptor kinase B, often mutated in certain breast cancers) at the N-terminus with the h38C2 catalytic antibody at the C-terminus. This allows for **site-specific conjugation** of cytotoxic drugs—here, monomethyl auristatin F (MMAF) with a non-cleavable β-lactam linker—to particular lysine residues (Lys99) in the antibody. The final molecule selectively binds to mutant TrkB present on cancer cells, is internalized via receptor-mediated endocytosis, and releases its cytotoxic payload intracellarly, leading to targeted cell death and sparing healthy tissue. The mechanism focuses on microtubule inhibition brought about by MMAF.
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