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A high-titer scalable Chinese hamster ovary transient expression platform for production of biotherapeutics.
Gonzalez-Rivera, Juan C; Galvan, Alberto; Ryder, Todd; Milman, Monica; Agarwal, Kitty; Kandari, Lakshmi; Khetan, Anurag.
Afiliação
  • Gonzalez-Rivera JC; Biologics Development, Bristol Myers Squibb, New Brunswick, New Jersey, USA.
  • Galvan A; Biologics Development, Bristol Myers Squibb, New Brunswick, New Jersey, USA.
  • Ryder T; Biologics Development, Bristol Myers Squibb, New Brunswick, New Jersey, USA.
  • Milman M; Biologics Development, Bristol Myers Squibb, New Brunswick, New Jersey, USA.
  • Agarwal K; Biologics Development, Bristol Myers Squibb, New Brunswick, New Jersey, USA.
  • Kandari L; Biologics Development, Bristol Myers Squibb, New Brunswick, New Jersey, USA.
  • Khetan A; Biologics Development, Bristol Myers Squibb, New Brunswick, New Jersey, USA.
Biotechnol Bioeng ; 121(11): 3454-3470, 2024 Nov.
Article em En | MEDLINE | ID: mdl-39101569
ABSTRACT
Transient gene expression (TGE) in Chinese hamster ovary (CHO) cells offers a route to accelerate biologics development by delivering material weeks to months earlier than what is possible with conventional cell line development. However, low productivity, inconsistent product quality profiles, and scalability challenges have prevented its broader adoption. In this study, we develop a scalable CHO-based TGE system achieving 1.9 g/L of monoclonal antibody in an unmodified host. We integrated continuous flow-electroporation and alternate tangential flow (ATF) perfusion to enable an end-to-end closed system from N-1 perfusion to fed-batch 50-L bioreactor production. Optimization of both the ATF operation for three-in-one application-cell growth, buffer exchange, and cell mass concentration-and the flow-electroporation process, led to a platform for producing biotherapeutics using transiently transfected cells. We demonstrate scalability up to 50-L bioreactor, maintaining a titer over 1 g/L. We also show comparable quality between both transiently and stably produced material, and consistency across batches. The results confirm that purity, charge variants and N-glycan profiles are similar. Our study demonstrates the potential of CHO-based TGE platforms to accelerate biologics process development timelines and contributes evidence supporting its feasibility for manufacturing early clinical material, aiming to strengthen endorsement for TGE's wider implementation.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Cricetulus / Reatores Biológicos / Anticorpos Monoclonais Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Cricetulus / Reatores Biológicos / Anticorpos Monoclonais Idioma: En Ano de publicação: 2024 Tipo de documento: Article