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Cysteine metabolic engineering and selective disulfide reduction produce superior antibody-drug-conjugates
Next-generation site-specific cysteine-based antibody–drug-conjugates (ADCs) broaden therapeutic index by precise drug-antibody attachments. However, manufacturing such ADCs for clinical validation requires complex full reduction and reoxidation processes, impacting product quality. To overcome this...
| Autores principales: | , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2022
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9068625/ https://www.ncbi.nlm.nih.gov/pubmed/35508689 http://dx.doi.org/10.1038/s41598-022-11344-z |
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| author | Procopio-Melino, Renée Kotch, Frank W. Prashad, Amar S. Gomes, Jose M. Wang, Wenge Arve, Bo Dawdy, Andrew Chen, Lawrence Sperry, Justin Hosselet, Christine He, Tao Kriz, Ronald Lin, Laura Marquette, Kimberly Tchistiakova, Lioudmila Somers, Will Rouse, Jason C. Zhong, Xiaotian |
| author_facet | Procopio-Melino, Renée Kotch, Frank W. Prashad, Amar S. Gomes, Jose M. Wang, Wenge Arve, Bo Dawdy, Andrew Chen, Lawrence Sperry, Justin Hosselet, Christine He, Tao Kriz, Ronald Lin, Laura Marquette, Kimberly Tchistiakova, Lioudmila Somers, Will Rouse, Jason C. Zhong, Xiaotian |
| author_sort | Procopio-Melino, Renée |
| collection | PubMed |
| description | Next-generation site-specific cysteine-based antibody–drug-conjugates (ADCs) broaden therapeutic index by precise drug-antibody attachments. However, manufacturing such ADCs for clinical validation requires complex full reduction and reoxidation processes, impacting product quality. To overcome this technical challenge, we developed a novel antibody manufacturing process through cysteine (Cys) metabolic engineering in Chinese hamster ovary cells implementing a unique cysteine-capping technology. This development enabled a direct conjugation of drugs after chemoselective-reduction with mild reductant tris(3-sulfonatophenyl)phosphine. This innovative platform produces clinical ADC products with superior quality through a simplified manufacturing process. This technology also has the potential to integrate Cys-based site-specific conjugation with other site-specific conjugation methodologies to develop multi-drug ADCs and exploit multi-mechanisms of action for effective cancer treatments. |
| format | Online Article Text |
| id | pubmed-9068625 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2022 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-90686252022-05-05 Cysteine metabolic engineering and selective disulfide reduction produce superior antibody-drug-conjugates Procopio-Melino, Renée Kotch, Frank W. Prashad, Amar S. Gomes, Jose M. Wang, Wenge Arve, Bo Dawdy, Andrew Chen, Lawrence Sperry, Justin Hosselet, Christine He, Tao Kriz, Ronald Lin, Laura Marquette, Kimberly Tchistiakova, Lioudmila Somers, Will Rouse, Jason C. Zhong, Xiaotian Sci Rep Article Next-generation site-specific cysteine-based antibody–drug-conjugates (ADCs) broaden therapeutic index by precise drug-antibody attachments. However, manufacturing such ADCs for clinical validation requires complex full reduction and reoxidation processes, impacting product quality. To overcome this technical challenge, we developed a novel antibody manufacturing process through cysteine (Cys) metabolic engineering in Chinese hamster ovary cells implementing a unique cysteine-capping technology. This development enabled a direct conjugation of drugs after chemoselective-reduction with mild reductant tris(3-sulfonatophenyl)phosphine. This innovative platform produces clinical ADC products with superior quality through a simplified manufacturing process. This technology also has the potential to integrate Cys-based site-specific conjugation with other site-specific conjugation methodologies to develop multi-drug ADCs and exploit multi-mechanisms of action for effective cancer treatments. Nature Publishing Group UK 2022-05-04 /pmc/articles/PMC9068625/ /pubmed/35508689 http://dx.doi.org/10.1038/s41598-022-11344-z Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
| spellingShingle | Article Procopio-Melino, Renée Kotch, Frank W. Prashad, Amar S. Gomes, Jose M. Wang, Wenge Arve, Bo Dawdy, Andrew Chen, Lawrence Sperry, Justin Hosselet, Christine He, Tao Kriz, Ronald Lin, Laura Marquette, Kimberly Tchistiakova, Lioudmila Somers, Will Rouse, Jason C. Zhong, Xiaotian Cysteine metabolic engineering and selective disulfide reduction produce superior antibody-drug-conjugates |
| title | Cysteine metabolic engineering and selective disulfide reduction produce superior antibody-drug-conjugates |
| title_full | Cysteine metabolic engineering and selective disulfide reduction produce superior antibody-drug-conjugates |
| title_fullStr | Cysteine metabolic engineering and selective disulfide reduction produce superior antibody-drug-conjugates |
| title_full_unstemmed | Cysteine metabolic engineering and selective disulfide reduction produce superior antibody-drug-conjugates |
| title_short | Cysteine metabolic engineering and selective disulfide reduction produce superior antibody-drug-conjugates |
| title_sort | cysteine metabolic engineering and selective disulfide reduction produce superior antibody-drug-conjugates |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9068625/ https://www.ncbi.nlm.nih.gov/pubmed/35508689 http://dx.doi.org/10.1038/s41598-022-11344-z |
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