Large scale controlled Fab exchange GMP process to prepare bispecific antibodies.

Autor:	Yao X; Tavotek Biotherapeutics, Suzhou, China., Xie M; Tavotek Biotherapeutics, Suzhou, China., Ben Y; Tavotek Biotherapeutics, Suzhou, China., Zhu Y; Bioworkshops (Suzhou) Limited, Suzhou, China., Yang G; Bioworkshops (Suzhou) Limited, Suzhou, China., Kwong SCW; Bioworkshops (Suzhou) Limited, Suzhou, China., Zhang Z; Bioworkshops (Suzhou) Limited, Suzhou, China., Chiu ML; Tavotek Biotherapeutics, Suzhou, China.; Tavotek Biotherapeutics, Lower Gwynedd, PA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in bioengineering and biotechnology [Front Bioeng Biotechnol] 2024 Jan 12; Vol. 11, pp. 1298890. Date of Electronic Publication: 2024 Jan 12 (Print Publication: 2023).
DOI:	10.3389/fbioe.2023.1298890
Abstrakt:	Objective: Bispecific antibodies (BsAbs) have demonstrated significant therapeutic impacts for the treatment of a broad spectrum of diseases that include oncology, auto-immune, and infectious diseases. However, the large-scale production of clinical batches of bispecific antibodies still has many challenges that include having low yield, poor stability, and laborious downstream purification processes. To address such challenges, we describe the optimization of the controlled Fab arm exchange (cFAE) process for the efficient generation of BsAbs. Methods: The process optimization of a large-scale good manufacturing practice (GMP) cFAE strategy to prepare BsAbs was based on screening the parameters of temperature, reduction, oxidation, and buffer exchange. We include critical quality standards for the reducing agent cysteamine hydrochloride. Results: This large-scale production protocol enabled the generation of bispecific antibodies with >90% exchange yield and at >95% purity. The subsequent downstream processing could use typical mAb procedures. Furthermore, we demonstrated that the bispecific generation protocol can be scaled up to ∼60 L reaction scale using parental monoclonal antibodies that were expressed in a 200 L bioreactor. Conclusion: We presented a robust development strategy for the cFAE process that can be used for a larger scale GMP BsAb production. Competing Interests: Authors XY, MX, YB, and MC were employed by Tavotek Biotherapeutics. Authors YZ, GY, SK, and ZZ were employed by Bioworkshops (Suzhou) Limited. (Copyright © 2024 Yao, Xie, Ben, Zhu, Yang, Kwong, Zhang and Chiu.)
Databáze:	MEDLINE
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