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Sigvotatug vedotin is an investigational antibody-drug conjugate (ADC) targeting integrin beta-6 (IB6), a cell surface receptor implicated in tumor pathogenesis and invasiveness. The drug consists of three main components: a humanized IgG1 monoclonal antibody directed against IB6, the cytotoxic payload monomethyl auristatin E (MMAE), and a protease-cleavable maleimidocaproyl-valine-citrulline (mc-vc) linker that attaches MMAE to the antibody. Upon binding to IB6-expressing tumor cells, the ADC is internalized and MMAE is released intracellularly, disrupting microtubule polymerization and inducing apoptosis. Sigvotatug vedotin is being developed primarily for non-small cell lung cancer (NSCLC) but is also under investigation for other solid tumors including head and neck squamous cell carcinoma, esophageal cancer, cutaneous squamous cell carcinoma, ovarian cancer, pancreatic adenocarcinoma, bladder cancer, cervical cancer, gastric cancer, HER2-negative breast cancer, gastroesophageal junction adenocarcinoma[1][4][5][6].
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