Interest in the use of antibody–drug conjugates (ADCs) for cancer therapy has increased recently, with two approved for clinical use. However, issues with the in vivo stability of the linkers used in many ADCs — based on maleimide-containing components conjugated to reactive thiols — have become apparent. To address this, Lyon et al. incorporated a basic functional group adjacent to the maleimide, which induced the thiosuccinimide ring to undergo rapid hydrolysis, protecting it from maleimide elimination reactions. This 'self-stabilizing' ADC exhibited improved antitumour activity and reduced bone marrow toxicity in mouse lymphoma xenograft models.