antibody-drug conjugate

An antibody-drug conjugate, or ADC, is a guided missile carrying a tiny but lethal payload. It pairs a monoclonal antibody, which homes in on a marker found on cancer cells, with a powerful cell-killing toxin attached by a chemical linker. The antibody is the guidance system, the toxin is the warhead, and the linker is what holds them together until delivery. The aim is to drop the poison onto the tumour while largely sparing healthy tissue.

An ADC has three engineered parts. The antibody binds a target antigen on the tumour cell surface; the whole complex is then drawn inside the cell; and the linker releases the cytotoxic payload, usually a drug far too toxic to give on its own, right where it can do the most damage. This combines the precision of targeted antibody therapy with the cell-killing punch of cytotoxic chemotherapy.

ADCs are not perfectly clean weapons. The toxin can leak before reaching the target, healthy cells bearing a little of the antigen can be hit, and tumour cells can lose the target over time, producing resistance. They therefore have their own toxicity profiles and require a target that is strongly present on the cancer. Examples include trastuzumab emtansine and trastuzumab deruxtecan for HER2-positive breast cancer, and brentuximab vedotin for certain lymphomas.