Antibody-Drug Conjugate (ADC) Research in Ophthalmology--a Review
Jie Shen1,2, Mayssa Attar3
1Department of Pharmacokinetics, Dynamics and Disposition, Allergan, Irvine, California, 92612, USA. shen_jie@allergan.com.
Abstract:
Similar to cancer, many ocular proliferative disorders could be treated with a specific antibody conjugated to a toxin. Active targeting to inhibit epithelial and endothelial cell proliferation in the eye has been tested using antibody-drug conjugates (ADC) both pre-clinically and clinically. Achieving efficacious drug concentrations in the eye, in particular to treat back of the eye disorders is challenging, and the promise of targeted antibody mediated delivery holds great potential. In this review, we describe the research efforts in drug targeting using ADC for the treatment of choroidal neovascularization (CNV), posterior lens capsule opacification, and proliferative vitreoretinopathy. Among these disorders, CNV represents a more active research focus, with more target antigens tested, given the disease prevalence and wider target antigen selection based on current understanding of the pathophysiology of the disease. However, the only research advancing to testing in clinical stage is for posterior lens capsule opacification. Compared to oncology, ADC research and development in ophthalmology is much more limited, possibly due to availability of successful therapies that could be administered locally with limited concern of off-target drug toxicity.
Insights
Antibody-drug conjugates (ADCs) show promise for treating eye disorders like choroidal neovascularization. While research is limited compared to cancer, ADCs offer targeted delivery for challenging back-of-the-eye conditions.
Area of Science:
- Ophthalmology
- Oncology
- Pharmacology
Background:
- Ocular proliferative disorders share similarities with cancers, suggesting antibody-drug conjugates (ADCs) as a potential therapeutic strategy.
- Targeted delivery of toxins via ADCs aims to inhibit aberrant cell proliferation in the eye.
- Achieving effective drug concentrations in the posterior segment of the eye remains a significant challenge.
Purpose of the Study:
- To review research on antibody-drug conjugates (ADCs) for treating ocular proliferative disorders.
- To highlight specific conditions such as choroidal neovascularization (CNV), posterior lens capsule opacification, and proliferative vitreoretinopathy.
- To compare the development status of ADCs in ophthalmology versus oncology.
Main Methods:
- Literature review of pre-clinical and clinical studies on ADCs in ophthalmology.
- Analysis of target antigens and disease pathophysiology for selected ocular disorders.
- Comparison of research progress and clinical translation between ophthalmology and oncology.
Main Results:
- Choroidal neovascularization (CNV) is a major research focus with multiple target antigens explored due to disease prevalence.
- Posterior lens capsule opacification is the only condition with research that has advanced to clinical trials.
- Ophthalmology exhibits significantly less ADC research and development compared to oncology, potentially due to existing local therapies with lower toxicity concerns.
Conclusions:
- ADCs hold significant potential for targeted therapy in various ocular proliferative disorders.
- Despite challenges, targeted antibody-mediated delivery offers a promising approach for treating back-of-the-eye diseases.
- Further research and development in ophthalmic ADCs are warranted, though progress is slower than in oncology.
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