SUSTAINED DELIVERY OF A MONOCLONAL ANTIBODY AGAINST SARS-COV-2 BY MICROENCAPSULATED CELLS: A PROOF-OF-CONCEPT STUDY
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Date
2022
Authors
Ashimova, Assem
Myngbay, Askhat
Yegorov, Sergey
Negmetzhanov, Baurzhan
Kadyrova, Irina
Yershova, Angelina
Kart, Ulpan
Miller, Matthew S.
Hortelano, Gonzalo
Journal Title
Journal ISSN
Volume Title
Publisher
Pharmaceutics
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.
Description
Keywords
Type of access: Open Access, COVID-19, SARS-CoV-2, IgG, monoclonal antibody, CR3022, cell encapsulation
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