vedotin

Vedotin is a class name used for antibody-drug conjugates (ADCs) that carry the cytotoxic payload monomethyl auristatin E (MMAE). The most well-known example is brentuximab vedotin, an ADC in which MMAE is attached to a monoclonal antibody that targets CD30 on certain lymphoma cells. The vedotin suffix is now seen in several MMAE-based ADCs targeting different antigens.

Mechanism of action involves targeted delivery: the antibody binds its tumor-associated antigen, the ADC is internalized, and the linker holding MMAE is cleaved inside the cell to release the active toxin. MMAE then disrupts microtubule polymerization, inhibiting cell division and triggering cell death in the targeted cancer cells. Because MMAE is extremely potent, the linker is designed to minimize release of the drug outside target cells.

Composition and linker details vary among vedotin-containing ADCs, but a common design uses an antibody linked to MMAE through a protease-cleavable dipeptide linker (often a valine-citrulline linker) with a self-immolative spacer. This arrangement allows stable circulation and selective intracellular release of MMAE after antigen binding and internalization.

Clinical use centers on CD30-expressing lymphomas for brentuximab vedotin, including classical Hodgkin lymphoma and systemic anaplastic large cell lymphoma, with additional approvals for other CD30-positive lymphomas in relapsed or refractory settings. Other vedotin-based ADCs (targeting different antigens) extend the approach to other cancer types.

Safety and tolerability reflect MMAE exposure and off-target effects, with commonly reported adverse events such as peripheral neuropathy, fatigue, nausea, neutropenia, and infections. As with all ADCs, treatment requires careful patient selection and monitoring.