vedotincontaining

Vedotin-containing refers to a subset of antibody-drug conjugates (ADCs) that use monomethyl auristatin E (MMAE) as the cytotoxic payload. In these molecules, MMAE is covalently linked to a monoclonal antibody or other targeting moiety via a protease-cleavable linker, most commonly a valine-citrulline dipeptide linker with a self-immolative spacer. After binding to the target antigen and internalization into cancer cells, lysosomal enzymes cleave the linker, releasing MMAE. The MMAE then inhibits tubulin polymerization, disrupting cell division and inducing cell death. This design aims to deliver a potent toxin selectively to tumor cells expressing the target antigen while limiting systemic exposure.

Notable vedotin-containing ADCs include brentuximab vedotin (targets CD30) for Hodgkin lymphoma and anaplastic large cell lymphoma; polatuzumab vedotin (targets CD79b) used in certain B-cell lymphomas in combination regimens; enfortumab vedotin (targets Nectin-4) for urothelial carcinoma; and tisotumab vedotin (targets Tissue Factor) for cervical cancer. These agents illustrate the progression of vedotin-based therapy from early approvals in 2011 to multiple products with diverse targets in the 2010s and 2020s. The development of vedotin-containing ADCs has been driven by improvements in linker chemistry, targeting specificity, and management of associated toxicities.

Common adverse effects across vedotin-containing ADCs include peripheral neuropathy, fatigue, nausea, cytopenias, and increased risk of infections. Some products have additional safety considerations, such as ocular toxicity with tisotumab vedotin. Dosing and scheduling vary by product and indication, reflecting differences in linker design, target antigen, and patient population.