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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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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
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author Tawfiq, Zhala
Caiazza, Nicky C.
Kambourakis, Spiros
Matsuda, Yutaka
Griffin, Benjamin
Lippmeier, J. Casey
Mendelsohn, Brian A.
author_facet Tawfiq, Zhala
Caiazza, Nicky C.
Kambourakis, Spiros
Matsuda, Yutaka
Griffin, Benjamin
Lippmeier, J. Casey
Mendelsohn, Brian A.
author_sort Tawfiq, Zhala
collection PubMed
description [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.
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spelling pubmed-71434112020-04-10 Synthesis and Biological Evaluation of Antibody Drug Conjugates Based on an Antibody Expression System: Conamax Tawfiq, Zhala Caiazza, Nicky C. Kambourakis, Spiros Matsuda, Yutaka Griffin, Benjamin Lippmeier, J. Casey Mendelsohn, Brian A. ACS Omega [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. American Chemical Society 2020-03-19 /pmc/articles/PMC7143411/ /pubmed/32280859 http://dx.doi.org/10.1021/acsomega.9b03628 Text en Copyright © 2020 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Tawfiq, Zhala
Caiazza, Nicky C.
Kambourakis, Spiros
Matsuda, Yutaka
Griffin, Benjamin
Lippmeier, J. Casey
Mendelsohn, Brian A.
Synthesis and Biological Evaluation of Antibody Drug Conjugates Based on an Antibody Expression System: Conamax
title Synthesis and Biological Evaluation of Antibody Drug Conjugates Based on an Antibody Expression System: Conamax
title_full Synthesis and Biological Evaluation of Antibody Drug Conjugates Based on an Antibody Expression System: Conamax
title_fullStr Synthesis and Biological Evaluation of Antibody Drug Conjugates Based on an Antibody Expression System: Conamax
title_full_unstemmed Synthesis and Biological Evaluation of Antibody Drug Conjugates Based on an Antibody Expression System: Conamax
title_short Synthesis and Biological Evaluation of Antibody Drug Conjugates Based on an Antibody Expression System: Conamax
title_sort synthesis and biological evaluation of antibody drug conjugates based on an antibody expression system: conamax
url 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
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