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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2020
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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. |
format | Online Article Text |
id | pubmed-7143411 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
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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