ArticleACS medicinal chemistry letters2025
Homogeneous Dual-Payload Antibody-Drug Conjugates Produced by Combined Distinct Conjugation Strategies.
Article in ACS medicinal chemistry letters, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Recent advances in function-enhanced antibody-drug conjugates: Antibody optimization and payload combination.Acta pharmacologica Sinica · 2026Article
- Igniting cold tumors: reprogramming the tumor immune microenvironment with dual-payload ADCs in combination with PD-L1&4-1BB bispecific antibodies.Journal for immunotherapy of cancer · 2026Article
- Formulation Matters: The Overlooked Engine of Stability and Success in Antibody-Drug Conjugates.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Frontiers in Antibody-Drug Conjugates: Mechanisms, Design Innovations, and Clinical Applications in Targeted Cancer Therapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Clinical advances and challenges of antibody-mediated targeted drug delivery in breast cancer therapeutics.Discover oncology · 2026Review
- A Dual-Payload Bispecific ADC Improved Potency and Efficacy over Single-Payload Bispecific ADCs.Pharmaceutics · 2025Article
- Antibody-drug conjugate: a newly developed biological missile for tumor treatment.Frontiers in oncology · 2025Review
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Authors and funding
6 authors.
Funding
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Abstract
Antibody-drug conjugates (ADCs) represent a promising class of targeted cancer therapies, combining monoclonal antibody specificity with cytotoxic drug potency. Despite significant ADC technology advancements, challenges such as limited efficacy, often attributed to tumor heterogeneity and resistance development, remain present. In this study, we developed homogeneous dual-payload ADCs by combining site-selective conjugation methods: second-generation AJICAP technology for lysine modification and conventional interchain-break conjugation. Using trastuzumab as a model antibody, we successfully synthesized a drug-to-antibody ratio (DAR) of 10 (2 + 8) dual-payload ADC with monomethyl auristatin E and deruxtecan, displaying low aggregation and stable physicochemical properties. The dual-payload ADC exhibited superior in vitro cytotoxicity against HER2-positive SKBR-3 cells, compared to T-DXd, and demonstrated enhanced tumor suppression in vivo in a NCI-N87 xenograft model. These results highlight the potential of multipayload ADCs in enhancing therapeutic efficacy while maintaining stability, thereby providing a new strategy to overcome traditional ADC-related limitations.
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