A series of groundbreaking publications in Nature Biotechnology introduce antibody–bottlebrush prodrugs as next-generation targeted cancer therapies. These constructs allow higher drug-to-antibody ratios and accommodate a broader range of drug payloads compared to traditional antibody-drug conjugates (ADCs), including the use of lower potency agents. Preclinical models demonstrate favorable efficacy and safety, marking a significant advance in therapeutic design enhancing precision oncology strategies.