Suitability of transiently expressed antibodies for clinical studies: product quality consistency at different production scales
Rodriguez-Conde, Sara; Inman, Sophie; Lindo, Viv; Amery, Leanne; Tang, Alison; Okorji-Obike, Uche; Du, Wenjuan; Bosch, Berend-Jan; Wichgers Schreur, Paul J; Kortekaas, Jeroen; Sola, Isabel; Enjuanes, Luis; Kerry, Laura; Mahal, Katharina; Hulley, Martyn; Daramola, Olalekan
(2022) mAbs, volume 14, issue 1, pp. 1 - 12
(Article)
Abstract
Transgenic human monoclonal antibodies derived from humanized mice against different epitopes of the Middle East respiratory syndrome coronavirus (MERS-CoV), and chimeric llama-human bispecific heavy chain-only antibodies targeting the Rift Valley fever virus (RVFV), were produced using a CHO-based transient expression system. Two lead candidates were assessed for each model virus
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before selecting and progressing one lead molecule. MERS-7.7G6 was used as the model antibody to demonstrate batch-to-batch process consistency and, together with RVFV-107-104, were scaled up to 200 L. Consistent expression titers were obtained in different batches at a 5 L scale for MERS-7.7G6. Although lower expression levels were observed for MERS-7.7G6 and RVFV-107-104 during scale up to 200 L, product quality attributes were consistent at different scales and in different batches. In addition to this, peptide mapping data suggested no detectable sequence variants for any of these candidates. Functional assays demonstrated comparable neutralizing activity for MERS-7.7G6 and RVFV-107-104 generated at different production scales. Similarly, MERS-7.7G6 batches generated at different scales were shown to provide comparable protection in mouse models. Our study demonstrates that a CHO-based transient expression process is capable of generating consistent product quality at different production scales and thereby supports the potential of using transient gene expression to accelerate the manufacturing of early clinical material.
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Keywords: CHO cells, MERS, RVFV, bunyavirus, coronavirus, product quality attributes, scalability, transient gene expression, virus, zoonosis, Immunology and Allergy, Immunology
ISSN: 1942-0862
Publisher: Landes Bioscience
Note: Funding Information: This study was financed by a grant from the Zoonotic Anticipation and Preparedness Initiative (ZAPI) project; which was funded by the Innovative Medicines Initiative (IMI, grant agreement no. 115760), the European Commission, and in-kind contributions from European Federation of Pharmaceutical Industries and Associations (EFPIA) partners. The authors would like to thank Dr. Michèle Bouloy (Institut Pasteur, France) who kindly provided the RVFV Clone 13. We also would like to thank all partners, scientists, post-docs, and graduate students involved in the ZAPI Project for their work and contributions, in particular: Paul Varley, Dorota Kozub, Gary Pettman, Maiken Kristiansen, Aled Charles, Kieran Mistry, Ainul Zulkepli, Stephanie Davies, Katie Day, Sofia Ekizoglou, Peng Ke, Bradley Rawlins, Evangelia Ttofi, Tom Witkos, Chloe Parry (AstraZeneca), Sandra van de Water (Wageningen Bioveterinary Research, the Netherlands) and Jean-Christophe Audonnet (Boehringer Ingelheim Animal Health, Global Innovation, France; ZAPI coordinator). Publisher Copyright: © 2022 AstraZeneca. Published with license by Taylor & Francis Group, LLC.
(Peer reviewed)