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Vincent Ling, Susan Elliott, Paul Stabila, Brenda Dean, Lisa D. Orecchio, Konrad Kauper, Cahil McGovern, Weng Tao; Antibody Scaffold-based Biotherapeutics Are Secreted From Ophthalmic Ect Devices. Invest. Ophthalmol. Vis. Sci. 2011;52(14):474.
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Proteins are a dominant class of therapeutics used in the treatment of eye diseases. However, large antibody based protein drugs are unable to bypass the blood-retinal barrier, and thus require repeated intraocular administration for treatment. We have previously demonstrated that the Neurotech encapsulated cell technology (ECT) intraocular devices can deliver a biotherapeutic directly to the eye consistently over the course of 2 years in human clinical trials, suggesting this technology may be extended to other ophthalmic biologics as well, for example those related to wet AMD.
cDNA sequences representing the major classes of antibody scaffold biologics were synthesized, including- full antibody, antibody Fab fragments, single chain (ScFv) antibodies, and fusion receptor-Fc molecules. cDNA expression vectors were used to create stable human cell lines secreting desired antibody-based biologics. Cell lines were subsequently encapsulated to create Neurotech ocular ECT implants. The rate of protein secretion was determined by ELISA.
Cultured clonal cell lines secreted all classes of antibody scaffold proteins, many on par with CHO-cell line based manufacturing systems. Clonal cell lines exhibited robust recombinant protein secretion, with levels of some cell lines approaching 200 - 20,000 ng/million cells/day (20 pcd). Cell lines producing active antibody scaffold based biologics were successfully encapsulated, and initial production of recombinant proteins from individual ECT devices were detected at levels up to 50 - 1000 ng/day.
Proof-of-concept studies suggest that Neurotech ECT devices may be an effective antibody scaffold-based drug delivery platform for ophthalmic indications.
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