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Sustained Delivery of a Monoclonal Antibody against SARS-CoV-2 by Microencapsulated Cells: A Proof-of-Concept Study
Background: Monoclonal antibody (mAb) therapy is a promising antiviral intervention for Coronovirus disease (COVID-19) with a potential for both treatment and prophylaxis. However, a major barrier to implementing mAb therapies in clinical practice is the intricate nature of mAb preparation and deliv...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9607555/ https://www.ncbi.nlm.nih.gov/pubmed/36297477 http://dx.doi.org/10.3390/pharmaceutics14102042 |
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author | Ashimova, Assem Myngbay, Askhat Yegorov, Sergey Negmetzhanov, Baurzhan Kadyrova, Irina Yershova, Angelina Kart, Ulpan Miller, Matthew S. Hortelano, Gonzalo |
author_facet | Ashimova, Assem Myngbay, Askhat Yegorov, Sergey Negmetzhanov, Baurzhan Kadyrova, Irina Yershova, Angelina Kart, Ulpan Miller, Matthew S. Hortelano, Gonzalo |
author_sort | Ashimova, Assem |
collection | PubMed |
description | Background: Monoclonal antibody (mAb) therapy is a promising antiviral intervention for Coronovirus disease (COVID-19) with a potential for both treatment and prophylaxis. However, a major barrier to implementing mAb therapies in clinical practice is the intricate nature of mAb preparation and delivery. Therefore, here, in a pre-clinical model, we explored the possibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mAb delivery using a mAb-expressing encapsulated cell system. Methods: Murine G-8 myoblasts were transfected with plasmids coding for the heavy and light chains of CR3022, a well-characterized SARS-CoV-2 mAb that targets the Spike receptor binding domain (RBD), and then encapsulated into alginate microcapsules. The microcapsules were then intraperitoneally implanted into immunocompetent (C57/BL6J) mice and changes in circulating CR3022 titres were assessed. The in vitro and ex vivo characterization of the mAb was performed using western blotting, RBD ELISA, and microscopy. Results: Transfected G-8 myoblasts expressed intact CR3022 IgG at levels comparable to transfected HEK-293 cells. Cell encapsulation yielded microcapsules harbouring approximately 1000 cells/capsule and sustainably secreting CR3022 mAb. Subsequent peritoneal G-8 microcapsule implantation into mice resulted in a gradual increase of CR3022 concentration in blood, which by day 7 peaked at 1923 [1656–2190] ng/mL and then gradually decreased ~4-fold by day 40 post-implantation. Concurrently, we detected an increase in mouse anti-CR3022 IgG titers, while microcapsules recovered by day 40 post-implantation showed a reduced per-microcapsule mAb production. Summary: We demonstrate here that cell microencapsulation is a viable approach to systemic delivery of intact SARS-CoV-2 mAb, with potential therapeutic applications that warrant further exploration. |
format | Online Article Text |
id | pubmed-9607555 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96075552022-10-28 Sustained Delivery of a Monoclonal Antibody against SARS-CoV-2 by Microencapsulated Cells: A Proof-of-Concept Study Ashimova, Assem Myngbay, Askhat Yegorov, Sergey Negmetzhanov, Baurzhan Kadyrova, Irina Yershova, Angelina Kart, Ulpan Miller, Matthew S. Hortelano, Gonzalo Pharmaceutics Article Background: Monoclonal antibody (mAb) therapy is a promising antiviral intervention for Coronovirus disease (COVID-19) with a potential for both treatment and prophylaxis. However, a major barrier to implementing mAb therapies in clinical practice is the intricate nature of mAb preparation and delivery. Therefore, here, in a pre-clinical model, we explored the possibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mAb delivery using a mAb-expressing encapsulated cell system. Methods: Murine G-8 myoblasts were transfected with plasmids coding for the heavy and light chains of CR3022, a well-characterized SARS-CoV-2 mAb that targets the Spike receptor binding domain (RBD), and then encapsulated into alginate microcapsules. The microcapsules were then intraperitoneally implanted into immunocompetent (C57/BL6J) mice and changes in circulating CR3022 titres were assessed. The in vitro and ex vivo characterization of the mAb was performed using western blotting, RBD ELISA, and microscopy. Results: Transfected G-8 myoblasts expressed intact CR3022 IgG at levels comparable to transfected HEK-293 cells. Cell encapsulation yielded microcapsules harbouring approximately 1000 cells/capsule and sustainably secreting CR3022 mAb. Subsequent peritoneal G-8 microcapsule implantation into mice resulted in a gradual increase of CR3022 concentration in blood, which by day 7 peaked at 1923 [1656–2190] ng/mL and then gradually decreased ~4-fold by day 40 post-implantation. Concurrently, we detected an increase in mouse anti-CR3022 IgG titers, while microcapsules recovered by day 40 post-implantation showed a reduced per-microcapsule mAb production. Summary: We demonstrate here that cell microencapsulation is a viable approach to systemic delivery of intact SARS-CoV-2 mAb, with potential therapeutic applications that warrant further exploration. MDPI 2022-09-24 /pmc/articles/PMC9607555/ /pubmed/36297477 http://dx.doi.org/10.3390/pharmaceutics14102042 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ashimova, Assem Myngbay, Askhat Yegorov, Sergey Negmetzhanov, Baurzhan Kadyrova, Irina Yershova, Angelina Kart, Ulpan Miller, Matthew S. Hortelano, Gonzalo Sustained Delivery of a Monoclonal Antibody against SARS-CoV-2 by Microencapsulated Cells: A Proof-of-Concept Study |
title | Sustained Delivery of a Monoclonal Antibody against SARS-CoV-2 by Microencapsulated Cells: A Proof-of-Concept Study |
title_full | Sustained Delivery of a Monoclonal Antibody against SARS-CoV-2 by Microencapsulated Cells: A Proof-of-Concept Study |
title_fullStr | Sustained Delivery of a Monoclonal Antibody against SARS-CoV-2 by Microencapsulated Cells: A Proof-of-Concept Study |
title_full_unstemmed | Sustained Delivery of a Monoclonal Antibody against SARS-CoV-2 by Microencapsulated Cells: A Proof-of-Concept Study |
title_short | Sustained Delivery of a Monoclonal Antibody against SARS-CoV-2 by Microencapsulated Cells: A Proof-of-Concept Study |
title_sort | sustained delivery of a monoclonal antibody against sars-cov-2 by microencapsulated cells: a proof-of-concept study |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9607555/ https://www.ncbi.nlm.nih.gov/pubmed/36297477 http://dx.doi.org/10.3390/pharmaceutics14102042 |
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