Mechanisms of action of monoclonal antibody (Ab) conjugates. Monoclonal antibodies and their fragments can be conjugated or linked to cytotoxic agents. Chemotherapy and toxin conjugates must be internalized via receptor-mediated endocytosis, whereas internalization is not required for radioisotope conjugates. After internalization, the active cytotoxic component is released and mediates cell death. Ricin-based immunotoxins depurinate ribosomal RNA and inhibit protein synthesis. Pseudomonas (PE)- and diphtheria (DT) -derived immunotoxins ADP ribosylate elongation factor-2 and inhibit protein synthesis. Antibody drug conjugates mediate cytotoxicity by drug-specific actions (eg, targeting tubulin by maytansin and auristatin, and induction of DNA breaks by calicheamicin). dgRTA, deglycosylated ricin A chain.