LUZ-Y,a Novel Platform for the Mammalian Cell Production of Full-length IgG-bispecific Antibodies |
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Authors: | Bernd J. Wranik Erin L. Christensen Gabriele Schaefer Janet K. Jackman Andrew C. Vendel Dan Eaton |
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Affiliation: | From the Departments of ‡Protein Chemistry.;§Research Oncology, and ;¶Discovery Immunology, Genentech, South San Francisco, California 94080 and ;the ‖Lilly Biotechnology Center-San Diego, San Diego, California 92121 |
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Abstract: | The ability of bispecific antibodies to simultaneously bind two unique antigens has great clinical potential. However, most approaches utilized to generate bispecific antibodies yield antibody-like structures that diverge significantly from the structure of archetype human IgG, and those that do approach structural similarity to native antibodies are often challenging to engineer and manufacture. Here, we present a novel platform for the mammalian cell production of bispecific antibodies that differ from their parental mAbs by only a single point mutation per heavy chain. Central to this platform is the addition of a leucine zipper to the C terminus of the CH3 domain of the antibody that is sufficient to drive the heterodimeric assembly of antibody heavy chains and can be readily removed post-purification. Using this approach, we developed various antibody constructs including one-armed Abs, bispecific antibodies that utilize a common light chain, and bispecific antibodies that pair light chains to their cognate heavy chains via peptide tethers. We have applied this technology to various antibody pairings and will demonstrate the engineering, purification, and biological activity of these antibodies herein. |
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Keywords: | Antibody Engineering Protein Engineering Protein Processing Protein Self-assembly Protein-Protein Interactions Bispecific Antibodies Leucine Zippers |
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