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Antibody-Drug Conjugate (ADC) Research in Ophthalmology—a Review

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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.

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References

  1. Sassoon I, Blanc V. Antibody-drug conjugate (ADC) clinical pipeline: a review. Methods Mol Biol. 2013;1045:1–27.

    Article  PubMed  Google Scholar 

  2. Jager RD, Mieler WF, Miller JW. Age-related macular degeneration. N Engl J Med. 2008;358(24):2606–17.

    Article  CAS  PubMed  Google Scholar 

  3. Shen WY, Yu MJ, Barry CJ, Constable IJ, Rakoczy PE. Expression of cell adhesion molecules and vascular endothelial growth factor in experimental choroidal neovascularisation in the rat. Br J Ophthalmol. 1998;82(9):1063–71.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Husain D, Ambati B, Adamis AP, Miller JW. Mechanisms of age-related macular degeneration. Ophthalmol Clin N Am. 2002;15(1):87–91.

    Article  Google Scholar 

  5. Mayo GL, Melendez RF, Kumar N, McKinnon SJ, Glickman RD. Antibody-targeted photodynamic therapy. Am J Ophthalmol. 2003;136:1151–2.

    Article  CAS  PubMed  Google Scholar 

  6. Li T, Zhang M, Han Y, Zhang H, Xu L, Xiang Y. Targeting therapy of choroidal neovascularization by use of polypeptide- and PEDF-loaded immunoliposomes under ultrasound exposure. J Huazhong Univ Sci Technolog Med Sci. 2010;30(6):798–803.

    Article  PubMed  Google Scholar 

  7. Dawson DW, Volpert OV, Gillis P, Crawford SE, Xu H, Benedict W, et al. Pigment epithelium-derived factor: a potent inhibitor of angiogenesis. Science. 1999;285(5425):245–8.

    Article  CAS  PubMed  Google Scholar 

  8. Kimura H, Yasukawa T, Tabata Y, Ogura Y. Drug targeting to choroidal neovascularization. Adv Drug Deliv Rev. 2001;52(1):79–91.

    Article  CAS  PubMed  Google Scholar 

  9. Friedlander M, Theesfeld CL, Sugita M, Fruttiger M, Thomas MA, Chang S, et al. Involvement of integrins alpha v beta 3 and alpha v beta 5 in ocular neovascular diseases. Proc Natl Acad Sci U S A. 1996;93(18):9764–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Yasukawa T, Kimura H, Tabata Y, Miyamoto H, Honda Y, Ikada Y, et al. Active drug targeting with immunoconjugates to choroidal neovascularization. Curr Eye Res. 2000;21(6):952–61.

    Article  CAS  PubMed  Google Scholar 

  11. Kamizuru H, Kimura H, Yasukawa T, Tabata Y, Honda Y, Ogura Y. Monoclonal antibody-mediated drug targeting to choroidal neovascularization in the rat. Invest Ophthalmol Vis Sci. 2001;42(11):2664–72.

    CAS  PubMed  Google Scholar 

  12. Brooks PC, Clark RA, Cheresh DA. Requirement of vascular integrin alpha v beta 3 for angiogenesis. Science. 1994;264(5158):569–71.

    Article  CAS  PubMed  Google Scholar 

  13. Comparison of Age-related Macular Degeneration Treatments Trials (CATT) Research Group, Martin DF, Maguire MG, Fine SL, Ying GS, Jaffe GJ, et al. Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: two-year results. Ophthalmology. 2012;119(7):1388–98.

    Article  Google Scholar 

  14. Goins KM, Ortiz JR, Fulcher SF, Handa JT, Jaffe GJ, Foulks GN, et al. Inhibition of proliferating lens epithelium with antitransferrin receptor immunotoxin. J Cataract Refract Surg. 1994;20(5):513–6.

    Article  CAS  PubMed  Google Scholar 

  15. Tarsio JF, Kelleher PJ, Tarsio M, Emery JM, Lam DM. Inhibition of cell proliferation on lens capsules by 4197X-ricin A immunoconjugate. J Cataract Refract Surg. 1997;23(2):260–6.

    Article  CAS  PubMed  Google Scholar 

  16. Behar-Cohen FF, David T, Buechler Y, Nova MP, Houston LL, Pouliquen YM, et al. Cytotoxic effects of FGF2-saporin on bovine epithelial lens cells in vitro. Invest Ophthalmol Vis Sci. 1995;36(12):2425–33.

    CAS  PubMed  Google Scholar 

  17. David T, Tassin J, Lappi DA, Baird A, Courtois Y. Biphasic effect of the mitotoxin bFGF-saporin on bovine lens epithelial cell growth: effect of cell density and extracellular matrix. J Cell Physiol. 1992;153(3):483–90.

    Article  CAS  PubMed  Google Scholar 

  18. Behar-Cohen FF, David T, D’Hermies F, Pouliquen YM, Buechler Y, Nova MP, et al. In vivo inhibition of lens regrowth by fibroblast growth factor 2-saporin. Invest Ophthalmol Vis Sci. 1995;36(12):2434–48.

    CAS  PubMed  Google Scholar 

  19. Kelleher PJ, Tarsio JF, Clark DS. Cytotoxic effects of a monoclonal antibody-ricin A immunotoxin on human ocular cells in culture. ARVO abstract 2562. Invest Ophthalmol Vis Sci. 1992;33:1168.

    Google Scholar 

  20. Crosson CE, Kelleher PJ, Lam DM. Ocular pharmacokinetics of lens epithelial cell-specific immunotoxin 4197X-RA. Exp Eye Res. 1992;55(1):87–91.

    Article  CAS  PubMed  Google Scholar 

  21. Clark DS, Emery JM, Munsell MF. Inhibition of posterior capsule opacification with an immunotoxin specific for lens epithelial cells: 24 month clinical results. J Cataract Refract Surg. 1998;24(12):1614–20.

    Article  CAS  PubMed  Google Scholar 

  22. Castillo E. MDX-RA Medarex Inc. IDrugs. 1998;1(4):476–9.

    CAS  PubMed  Google Scholar 

  23. Meacock WR, Spalton DJ, Hollick EJ, Boyce JF, Barman S, Sanguinetti G. Double-masked prospective ocular safety study of a lens epithelial cell antibody to prevent posterior capsule opacification. J Cataract Refract Surg. 2000;26(5):716–21.

    Article  CAS  PubMed  Google Scholar 

  24. PR Newswire. Medarex suspends patient enrollment in phase III trial of MDX-RA cataract product. 1998 December 15. Available from: http://www.thefreelibrary.com/_/print/PrintArticle.aspx?id=53401608.

  25. Elgohary MA, Dowler JG. Incidence and risk factors of Nd:YAG capsulotomy after phacoemulsification in non-diabetic and diabetic patients. Clin Experiment Ophthalmol. 2006;34(6):526–34.

    PubMed  Google Scholar 

  26. Schubert HD. Vitreoretinal changes associated with rise in intraocular pressure after Nd:YAG capsulotomy. Ophthalmic Surg. 1987;18(1):19–22.

    CAS  PubMed  Google Scholar 

  27. Sadaka A, Giuliari GP. Proliferative vitreoretinopathy: current and emerging treatments. Clin Ophthalmol. 2013;6:1325–33.

    Google Scholar 

  28. Zhang W, Tan J, Liu Y, Li W, Gao Q, Lehmann PV. Assessment of the innate and adaptive immune system in proliferative vitreoretinopathy. Eye. 2012;26(6):872–81.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Jaffe GJ, Earnest K, Fulcher S, Lui GM, Houston LL. Antitransferrin receptor immunotoxin inhibits proliferating human retinal pigment epithelial cells. Arch Ophthalmol. 1990;108(8):1163–8.

    Article  CAS  PubMed  Google Scholar 

  30. Baudouin C, Brignole F, Fredj-Reygrobellet D, Nègre F, Bayle J, Gastaud P. Transferrin receptor expression by retinal pigment epithelial cells in proliferative vitreoretinopathy. Invest Ophthalmol Vis Sci. 1992;33(10):2822–9.

    CAS  PubMed  Google Scholar 

  31. Hermsen VM, Fulcher SF, Spiekerman M, Phinizy JL, Di Tullio NW. Long-term inhibition of cellular proliferation by immunotoxins. Arch Ophthalmol. 1990;108(7):1009–11.

    Article  CAS  PubMed  Google Scholar 

  32. Handa JT, Houston LL, Jaffe GJ. The antiproliferative effect of a transferrein-toxin on human retinal pigment epithelial cells and rabbit fibroblasts. Invest Ophthalmol Vis Sci. 1993;34(12):3419–28.

    CAS  PubMed  Google Scholar 

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Correspondence to Jie Shen.

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Shen, J., Attar, M. Antibody-Drug Conjugate (ADC) Research in Ophthalmology—a Review. Pharm Res 32, 3572–3576 (2015). https://doi.org/10.1007/s11095-015-1728-9

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  • DOI: https://doi.org/10.1007/s11095-015-1728-9

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