The next generation of antibody–drug conjugates
Nature Medicine, Published online: 03 August 2026; doi:10.1038/s41591-026-04543-y The authors outline strategies to maximize the impact of ADCs by integrating multiple chemistry advances into drug constructs, and developing infrastructures and tools to accelerate and de-risk the preclinical and early clinical development of these agents.
Antibody-drug conjugates (ADCs)—which consist of a monoclonal antibody connected to a toxic payload—are engineered to administer high doses of cytotoxic agents to cancer cells. Ongoing research into ADC mechanisms and resistance in patients has led to significant advancements in ADC chemistry and therapeutic combinations. However, the rapid pace of innovation now outstrips clinical trial capacity, and individual modifications or combinations are unlikely to yield clinically meaningful benefits.
Therefore, the need arises to integrate multiple chemistry advances into single ADCs and develop frameworks, infrastructure, and tools to expedite and reduce the risk of preclinical and early clinical development of these agents. Furthermore, the creation of multidimensional molecular tools to predict ADC sensitivity, alongside the judicious use of new ADCs in early-stage cancers, could lead to improved patient outcomes.
The authors predict that in the future, developing diverse ADC libraries featuring distinct constructs and drug-to-antibody ratios will facilitate personalized treatment strategies tailored to individual tumor biology.
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