Transgenic Plant Technology for Producing Therapeutic Recombinant Antibodies

DESCRIPTION (provided by applicant): The need to develop novel, cost effective manufacturing processes to produce therapeutic antibodies commercially will continue to be of considerable and growing interest to biopharmaceutical and medical industries. The long-term objectives related to this application are to develop novel manufacturing processes using stable transgenic plants, namely Arabidopsis and lettuce, to improve the production process and demonstrate the feasibility and advantages of the manufacturing technology. These objectives are best accomplished by developing high yielding transgenic plants producing a model antibody and demonstrating the antibody's functionality by extensive characterization and testing in comparison with the same antibody produced in mammalian cell culture. The model antibody used for assessing the technology and comparison purposes is a fully humanized IgGlK anti-tissue factor antibody (hOAT) that is currently in pre-clinical development as an anti-cancer therapeutic. The specific aims of this research proposal are to: i) develop lines of stable transgenic Arabidopsis and lettuce producing high yields of hOAT and produce 100 mg of hOAT antibody produced by stable transgenic lettuce; and ii) characterize the plant-derived hOAT to evaluate comparability to CHO-produced hOAT using in vitro testing (activity, protein characteristics), pharmacokinetics and in vivo anti-cancer efficacy in a mouse xenograft model. The plant-based system described would be one oUhe most economical processes for antibody production and could make it possible to produce these therapeutic proteins at significantly lower cost of goods, enabling wider spread use of antibody therapeutics, particularly in less economically developed markets. The use of hOAT as model protein will provide proof-of-principle, demonstrate production economics and antibody functionality/efficacy and also lead to a plant-derived antibody product that could be advanced into clinical studies.