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K. Kauper, P. Stabila, S. Elliot, M. Rivera, P. Heatherton, S. Sherman, C. McGovern, M. Stiles, B. Dean, W. Tao; Sustained Intraocular Delivery of a Receptor Antibody Using an Encapsulated Cell Technology Implant. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5317.
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The goal of the Neurotech's Encapsulated Cell Technology (ECT) is to deliver therapeutic factors produced by the encapsulated cells de novo over an extended implantation period mitigating the requirements of standard delivery modalities such as chronic repeated intraocular injections. To improve current standard of care in diseases such as age-related neovascularization and diabetic macular edema, sustained delivery of a receptor antibody at daily concentrations of nanograms, and preferably, micrograms per day over the course of months to years may be necessary. This study reports on the development of a cell encapsulated delivery system capable of sustained intraocular delivery of a receptor antibody.
Human ARPE-19 cells were genetically engineered to constitutively secrete a growth-factor neutralizing antibody. The expressed protein was assayed by ELISA, Western blot analysis, and preliminary binding affinity was determined. The engineered cells were then encapsulated in a polymer membrane capsule, implanted into the rabbit vitreous over a 3-month period and, subsequently, evaluated for intraocular secretion levels of the receptor antibody as well as for viability of the encapsulated cells.
Stable cell culture growth kinetics and viability and secretion of receptor antibody of unencapsulated cells were determined over 45 passages following thaw of a working and master cell bank. Binding studies reveal similar affinity to tested controls. In vitro encapsulated cells produced receptor antibody at levels in micrograms per capsule per day. Explanted devices maintained microgram levels of protein secretion with no indication of protein expression down-regulation compared to the in vitro held ECT capsules. Excellent encapsulated cell viability was maintained throughout the course of the implant period and based upon these results significantly longer implant stability and receptor antibody secretion is expected.
ECT technology is capable of secreting antibody-sized proteins and maintaining the intraocular secretion rates of these proteins in micrograms per day levels. Long-term intraocular delivery of receptor antibody may be of significant importance in improving chronic therapeutic treatments for diseases such as age-related neovascularization and diabetic macular edema.
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