Recent advances in function-enhanced antibody-drug conjugates: Antibody optimization and payload combination
Xin-Tong Liu1,2, Feng Tang3,4,5, Wei Huang6,7,8,9
1Nottingham Ningbo China Beacons of Excellence Research and Innovation Institute, University of Nottingham Ningbo China, Ningbo, 315100, China.
Acta Pharmacologica Sinica
|July 16, 2026
Summary
Next-generation antibody-drug conjugates (ADCs) enhance tumor therapy by improving bispecific construction, internalization, binding affinity, and payload innovation to overcome challenges of current treatments.
Area of Science:
- Oncology
- Pharmacology
- Biotechnology
Background:
- Antibody-drug conjugates (ADCs) represent a significant advancement in cancer therapeutics, combining targeted antibody delivery with potent cytotoxic payloads.
- Over 20 ADCs are approved, with >300 candidates in clinical trials, highlighting their therapeutic importance in hematological malignancies and solid tumors.
- Traditional ADCs face challenges including antigen heterogeneity, poor internalization, drug resistance, and toxicity.
Purpose of the Study:
- To review the latest advancements in next-generation antibody-drug conjugates (ADCs).
- To focus on design optimization strategies that enhance ADC function and overcome limitations of earlier generations.
- To explore four key areas of innovation: bispecific ADC construction, improved internalization, enhanced binding affinity, and novel payload combinations.
Main Methods:
- Literature review of recent research and clinical trial data on antibody-drug conjugates.
- Analysis of design strategies for next-generation ADCs.
- Focus on advancements in bispecific antibody engineering, internalization mechanisms, antibody affinity modulation, and payload diversification.
Main Results:
- Next-generation ADCs are being developed with enhanced targeting and efficacy through innovative design.
- Strategies include bispecific antibodies for broader targeting, optimized linker-payload systems for improved internalization and reduced resistance.
- Enhanced binding affinity and novel payload combinations aim to increase therapeutic index and overcome resistance mechanisms.
Conclusions:
- Next-generation ADCs show promise in overcoming the limitations of traditional antibody-drug conjugates.
- Continued innovation in ADC design, including bispecificity, internalization efficiency, binding affinity, and payload strategies, is crucial for advancing cancer therapy.
- These functional enhancements are expected to improve treatment outcomes and broaden the applicability of ADCs in oncology.
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