Advanced dual-payload antibody-drug conjugates (DualADCs) for targeted cancer chemo-immunotherapy

In this study, we developed novel dual-payload ADC (DualADC) platforms that enable co-delivery of a chemotherapeutic agent for direct tumor cell killing and a toll-like receptor agonist to stimulate antitumor immunity. Using triple-negative breast cancer (TNBC) as a model, we established advanced cysteine/lysine co-conjugation strategies optimized for antibody–drug ratio (ADR) and drug–drug ratio (DDR).

These refinements minimized hydrophobicity-induced precipitation, enhanced conjugation efficiency, and improved formulation stability. In vivo evaluations in two xenograft mouse models demonstrated strong antitumor efficacy, highlighting the therapeutic potential of DualADCs as a next-generation approach for synergistic chemo-immunotherapy.