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Objectives <p>The present review aims to provide comprehensive bench-to-bedside insights into ADC-related ocular toxicity for drug designers, pharmaceutical manufacturers, toxicologists, and medical staff, thereby enhancing the safety of ADC therapeutic applications.</p> Methods <p>The review comprehensively analyzes the recent progress in the pathological mechanisms of ADC-related ocular toxicity, evaluates existing non-clinical risk assessment strategies based on animal toxicological studies, and highlights future optimization directions. It also summarizes clinical adverse events to demonstrate the typical profile of ocular surface toxicity and provides clinical management strategies.</p> Results <p>ADC ocular toxicity primarily affects the ocular surface via on-target (antibody-mediated) and off-target (non-specific uptake) mechanisms. Key determinants include payload type (e.g., MMAF and DM4, which exhibit higher toxicity due to intracellular retention), linker properties (cleavable linkers mitigate off-target effects), and ADCs' physicochemical characteristics. Non-clinical models effectively predict corneal injury but poorly recapitulate conjunctival responses. Clinical management relies on early ophthalmic monitoring and dose adjustment, with 42.9%–100% of adverse events being reversible.</p> Conclusion <p>This review offers valuable insights into ADC ocular toxicity, emphasizing the importance of early-stage selection and optimization of ADCs and their components to reduce ocular toxicity risks. It provides a reference for mitigating ADC-related ocular toxicity risks and facilitates the future development of ADCs with improved safety and efficacy.</p>

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Bench-to-Bedside Perspectives on Ocular Toxicity of Antibody–Drug Conjugates: Toxicology, Clinical Management and Molecule Optimization

  • 期刊论文

  • 发表日期：

    2026年1月15日

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  • Jialing Zhang,
  • Weiyu Li,
  • Meng Li,
  • Gang Wu,
  • Yongbo Ni,
  • Jialiang Du,
  • Gangling Xu,
  • Maoqin Duan,
  • Yalan Yang,
  • Xiaojuan Yu,
  • Chunbo Cui,
  • Chunyu Liu,
  • Chuanfei Yu,
  • Lan Wang

摘要

Objectives

The present review aims to provide comprehensive bench-to-bedside insights into ADC-related ocular toxicity for drug designers, pharmaceutical manufacturers, toxicologists, and medical staff, thereby enhancing the safety of ADC therapeutic applications.

Methods

The review comprehensively analyzes the recent progress in the pathological mechanisms of ADC-related ocular toxicity, evaluates existing non-clinical risk assessment strategies based on animal toxicological studies, and highlights future optimization directions. It also summarizes clinical adverse events to demonstrate the typical profile of ocular surface toxicity and provides clinical management strategies.

Results

ADC ocular toxicity primarily affects the ocular surface via on-target (antibody-mediated) and off-target (non-specific uptake) mechanisms. Key determinants include payload type (e.g., MMAF and DM4, which exhibit higher toxicity due to intracellular retention), linker properties (cleavable linkers mitigate off-target effects), and ADCs' physicochemical characteristics. Non-clinical models effectively predict corneal injury but poorly recapitulate conjunctival responses. Clinical management relies on early ophthalmic monitoring and dose adjustment, with 42.9%–100% of adverse events being reversible.

Conclusion

This review offers valuable insights into ADC ocular toxicity, emphasizing the importance of early-stage selection and optimization of ADCs and their components to reduce ocular toxicity risks. It provides a reference for mitigating ADC-related ocular toxicity risks and facilitates the future development of ADCs with improved safety and efficacy.