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Synthesis and Biological Evaluation of Antibody Drug Conjugates Based on an Antibody Expression System: Conamax

[Image: see text] Antibody production for ADCs (or in general) is commonly performed by CHO-based platforms and limited by volumetric productivity, expensive downstream purification, and extended optimization timelines. The Conamax platform is a novel microbial-based protein production and secretion...

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Detalles Bibliográficos
Autores principales: Tawfiq, Zhala, Caiazza, Nicky C., Kambourakis, Spiros, Matsuda, Yutaka, Griffin, Benjamin, Lippmeier, J. Casey, Mendelsohn, Brian A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2020
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7143411/
https://www.ncbi.nlm.nih.gov/pubmed/32280859
http://dx.doi.org/10.1021/acsomega.9b03628
Descripción
Sumario:[Image: see text] Antibody production for ADCs (or in general) is commonly performed by CHO-based platforms and limited by volumetric productivity, expensive downstream purification, and extended optimization timelines. The Conamax platform is a novel microbial-based protein production and secretion system. A suite of synthetic biology tools have enabled high volumetric productivity (>1 g/L/d) and glycoengineering to produce simple and consistent human-like post-translational modifications. Conamax can be engineered to secrete genuine, functional monoclonal antibodies that have been successfully used to make antibody drug conjugates (ADCs) via cysteine-linked conjugation. Specifically, we evaluated ADCs derived from both a Conamax-produced anti-HER2 antibody and comparable commercially sourced Chinese hamster ovary (CHO)-produced material in an NCI-N87 gastric cancer xenograft model. Conjugation efficiency and resulting analytical data indicated comparable ADC quality and attributes. No statistical difference was observed between Conamax- and CHO-derived test articles thereby indicating similar efficacy and function. These results further demonstrate the potential of Conamax as a useful platform for the discovery and production of therapeutic antibodies and ADCs.