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Nat. Rev. Clin. Oncol. doi:10.1038/nrclinonc.2017.95 Figure 2 Antibody–drug conjugate therapies and their mechanisms of action Figure 2 | Antibody–drug conjugate therapies and their mechanisms of action. Antibody–drug conjugate (ADC) therapeutics incorporate three elements: a targeting antibody, a linker and a cytotoxic payload. Depending on the payload, ADCs can be classified into cytotoxic ADCs (with drug payload shown as a red sphere), immunotoxins with a bacterial toxin payload (blue sphere), or radioimmunotherapies with a radioactive isotope payload (indicated by radioactivity symbol). The mechanism of action of cytotoxic ADCs and immunotoxins is depicted: these agents bind to the cell surface, undergo internalisation, are trafficked to lysosomes, degraded, and the payload is subsequently released. Commonly used toxins, such as microtubule-disrupting agents or inhibitors of protein translation, are shown. Another possibility is the use of ADCs or immunotoxins with payloads that cause DNA damage. Radioimmunotherapy can target cell-surface receptors (such as EGFR) or extracellular targets, such as tenascin, and subsequently cause damage to cellular structures, such as DNA and mitochondria. Certain drugs, including antitumour antibiotics such as calicheamicins or pyrrolobenzodiazepines, can also cause DNA damage121 (not shown). Gan, H. K. et al. (2017) Antibody–drug conjugates in glioblastoma therapy: the right drugs to the right cells Nat. Rev. Clin. Oncol. doi:10.1038/nrclinonc.2017.95