Next‐Generation Antibody–Drug Conjugate Technologies

Antibody-drug conjugates (ADC) exploit the targeting specificity of antibodies to selectively deliver pharmacologically active small molecules to a diseased cell or tissue, thereby minimizing untoward effects on healthy tissues. Newer ADC entrants into the clinic have contained introduced cysteines for site-specific conjugation and/or new classes of DNA-damaging agents. This chapter summarizes key technology innovations that have shown preclinical promise and appear poised for translation into the clinic. The innovations encompass additional cytotoxic drug classes such as tubulysins, symmetric, and asymmetric benzodiazepine dimers, anthracyclines, and amatoxins. The clinical success of auristatin- and maytansinoid-based ADCs has spurred the evaluation of additional tubulin-targeting payloads. Innovations in drug-linker chemistry have been complemented by novel approaches to engineer antibodies in order to facilitate drug conjugation. The rapid expansion and refinement of ADC modalities hold great promise for improving care of diverse human diseases.