Bispecific antibody-drug conjugates: a modular blueprint for next-generation cancer therapeutics

Antibody-drug conjugates (ADCs) have rapidly developed over the past two decades as a class of targeted anticancer agents. These drugs deliver highly cytotoxic payloads conjugated to specific antibodies, targeting cancer cells and releasing the payload intracellularly to selectively kill tumor cells. However, in clinical practice, the therapeutic efficacy of ADCs is often inconsistent due to factors such as off-target effects, limited endocytosis rates, and the narrow specificity of the target. Bispecific antibody-drug conjugates (BsADCs) combine the characteristics of bispecific antibodies and ADCs, offering enhanced recognition capabilities and facilitating faster drug internalization, thereby potentially improving the therapeutic index and addressing some of the limitations of traditional ADCs. Moreover, BsADCs have the potential to treat not only cancer but also other diseases, positioning them as a future direction for ADC development.This review provides a brief overview of the structure of ADCs and current clinical research results. It focuses on the "toolbox" components of BsADCs and highlights examples of how each component is applied in the construction of BsADCs. This review also summarizes the key characteristics required for bispecific antibodies used in BsADC construction. Finally, a detailed analysis of the advantages of BsADCs over traditional ADCs is presented, along with a discussion of their future development. This paper aims to provide researchers interested in ADCs and BsADCs with detailed information on the composition, structure, and applications (including clinical data) of both ADCs and BsADCs, helping readers quickly understand the features and research progress of BsADCs and paving the way for further exploration in this field.