Nectin-4. a cell adhesion molecule belonging to the nectin family, plays a role in cell-cell junction formation and signaling. It is physiologically expressed in epithelial tissues but is frequently overexpressed in various cancers, including urothelial, breast, and lung carcinomas. This tumor-specific overexpression makes Nectin-4 an attractive therapeutic target.
Nectin-4-targeting antibodies, particularly antibody-drug conjugates (ADCs), have gained prominence in oncology. Enfortumab vedotin, an ADC composed of a monoclonal antibody against Nectin-4 linked to the cytotoxic agent monomethyl auristatin E (MMAE), is a landmark example. Approved for metastatic urothelial cancer, it selectively delivers chemotherapy to Nectin-4-expressing tumor cells, minimizing systemic toxicity.
Mechanistically, the antibody binds to Nectin-4 on cancer cells, triggering internalization and intracellular release of MMAE, which disrupts microtubules and induces apoptosis. Clinical trials demonstrated significant response rates and prolonged survival in refractory patients. However, challenges like acquired resistance and side effects (e.g., skin rash, neuropathy) underscore the need for further optimization.
Research continues to explore Nectin-4 antibodies in combination therapies and other cancer types, leveraging their potential for precision oncology while addressing current limitations.