Nature Biotechnology
23, 1159 - 1169 (2005)
Published online: 28 August 2005; | doi:10.1038/nbt1132
Production of human monoclonal antibody in eggs of chimeric chickensLei Zhu1, Marie-Cecile van de Lavoir1, Jenny Albanese2, David O Beenhouwer4, 5, Pina M Cardarelli2, Severino Cuison2, David F Deng1, Shrikant Deshpande2, Jennifer H Diamond1, Lynae Green2, Edward L Halk2, Babette S Heyer1, Robert M Kay1, Allyn Kerchner1, Philip A Leighton1, Christine M Mather1, Sherie L Morrison4, Zivko L Nikolov3, David B Passmore2, Alicia Pradas-Monne1, Benjamin T Preston2, Vangipuram S Rangan2, Mingxia Shi1, Mohan Srinivasan2, Steven G White3, Peggy Winters-Digiacinto1, Susan Wong2, Wen Zhou1
& Robert J Etches11
Origen Therapeutics, 1450 Rollins Road, Burlingame, California 94010, USA. 2
Medarex Inc., 521 Cottonwood Drive, Milpitas, California 95035, USA. 3
Department of Biological and Agricultural Engineering, Texas A&M University, College Station, Texas 77843, USA. 4
Department of Microbiology, Immunology and Molecular Genetics and the Molecular Biology Institute, University of California Los Angeles, Los Angeles, California 90095, USA. 5
Division of Infectious Diseases, VA Greater Los Angeles Healthcare System, Los Angeles, California 90073, USA.
Correspondence should be addressed to Robert J Etches retches@origentherapeutics.com The tubular gland of the chicken oviduct is an attractive system for protein expression as large quantities of proteins are deposited in the egg, the production of eggs is easily scalable and good manufacturing practices for therapeutics from eggs have been established. Here we examined the ability of upstream and downstream DNA sequences of ovalbumin, a protein produced exclusively in very high quantities in chicken egg white, to drive tissue-specific expression of human mAb in chicken eggs. To accommodate these large regulatory regions, we established and transfected lines of chicken embryonic stem (cES) cells and formed chimeras that express mAb from cES cell−derived tubular gland cells. Eggs from high-grade chimeras contained up to 3 mg of mAb that possesses enhanced antibody-dependent cellular cytotoxicity (ADCC), nonantigenic glycosylation, acceptable half-life, excellent antigen recognition and good rates of internalization.
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