Efficient production of bispecific antibody by FAST-Ig^TM and its application to NXT007 for the treatment of hemophilia A.

ABSTRACT: Efficient production of bispecific antibodies (BsAbs) in single mammalian cells is essential for basic research and industrial manufacturing. However, preventing unwanted pairing of heavy chains (HCs) and light chains (LCs) is a challenging task. To address this, we created an engineering technology for preferential cognate HC/LC and HC/HC paring called FAST-Ig (Four-chain Assembly by electrostatic Steering Technology - Immunoglobulin), and applied it to NXT007, a BsAb for the treatment of hemophilia A. We introduced charged amino-acid substitutions at the HC/LC interface to facilitate the proper assembly for manufacturing a standard IgG-type BsAb. We generated CH1/CL interface-engineered antibody variants that achieved > 95% correct HC/LC pairing efficiency with favorable pharmacological

SUBMITTER: Koga H 

PROVIDER: S-EPMC10283433 | biostudies-literature | 2023 Jan-Dec

REPOSITORIES: biostudies-literature