SUSTAINED DELIVERY OF A MONOCLONAL ANTIBODY AGAINST SARS-COV-2 BY MICROENCAPSULATED CELLS: A PROOF-OF-CONCEPT STUDY
| dc.contributor.author | Ashimova, Assem | |
| dc.contributor.author | Myngbay, Askhat | |
| dc.contributor.author | Yegorov, Sergey | |
| dc.contributor.author | Negmetzhanov, Baurzhan | |
| dc.contributor.author | Kadyrova, Irina | |
| dc.contributor.author | Yershova, Angelina | |
| dc.contributor.author | Kart, Ulpan | |
| dc.contributor.author | Miller, Matthew S. | |
| dc.contributor.author | Hortelano, Gonzalo | |
| dc.date.accessioned | 2023-06-30T09:17:14Z | |
| dc.date.available | 2023-06-30T09:17:14Z | |
| dc.date.issued | 2022 | |
| dc.description.abstract | 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. | en_US |
| dc.identifier.citation | Ashimova, A. N., Myngbay, A., Yegorov, S., Negmetzhanov, B., Kadyrova, I., Yershova, A., Kart, U., Miller, M. J., & Hortelano, G. (2022). Sustained Delivery of a Monoclonal Antibody against SARS-CoV-2 by Microencapsulated Cells: A Proof-of-Concept Study. Pharmaceutics, 14(10), 2042. https://doi.org/10.3390/pharmaceutics14102042 | en_US |
| dc.identifier.uri | http://nur.nu.edu.kz/handle/123456789/7279 | |
| dc.language.iso | en | en_US |
| dc.publisher | Pharmaceutics | en_US |
| dc.rights | Attribution-NonCommercial-ShareAlike 3.0 United States | * |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/3.0/us/ | * |
| dc.subject | Type of access: Open Access | en_US |
| dc.subject | COVID-19 | en_US |
| dc.subject | SARS-CoV-2 | en_US |
| dc.subject | IgG | en_US |
| dc.subject | monoclonal antibody | en_US |
| dc.subject | CR3022 | en_US |
| dc.subject | cell encapsulation | en_US |
| dc.title | SUSTAINED DELIVERY OF A MONOCLONAL ANTIBODY AGAINST SARS-COV-2 BY MICROENCAPSULATED CELLS: A PROOF-OF-CONCEPT STUDY | en_US |
| dc.type | Article | en_US |
| workflow.import.source | science |