Dataset Information

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 properties and developability. Among these, we selected a design (C3) that allowed us to separate the mis-paired species with an unintended pharmacological profile using ion-exchange chromatography. Crystal structure analysis demonstrated that the C3 design did not affect the overall structure of both Fabs. To determine the final design for HCs-heterodimerization, we compared the stability of charge-based and knobs into hole-based Fc formats in acidic conditions and selected the more stable charge-based format. FAST-Ig was also applicable to stable CHO cell lines for industrial production and demonstrated robust chain pairing with different subclasses of parent BsAbs. Thus, it can be applied to a wide variety of BsAbs both preclinically and clinically.

SUBMITTER: Koga H

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

REPOSITORIES: biostudies-literature

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

Koga Hikaru H Yamano Takashi T Betancur Juan J Nagatomo Satoko S Ikeda Yousuke Y Yamaguchi Kazuki K Nabuchi Yoshiaki Y Sato Kazuki K Teranishi-Ikawa Yuri Y Sato Motohiko M Hirayama Hiroyuki H Hayasaka Akira A Torizawa Takuya T Haraya Kenta K Sampei Zenjiro Z Shiraiwa Hirotake H Kitazawa Takehisa T Igawa Tomoyuki T Kuramochi Taichi T

mAbs 20230101 1

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 hemop ...[more]

PMID: 37339067

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

Publications

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

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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