Sustained Delivery of a Monoclonal Antibody against SARS-CoV-2 by Microencapsulated Cells: A Proof-of-Concept Study

Ashimova A. Myngbay A. Yegorov S. Negmetzhanov B. Kadyrova I. Yershova A. Kart U. Miller M.S. Hortelano G.
October 2022 MDPI

Pharmaceutics
2022 #14 Issue 10

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.

cell encapsulation , COVID-19 , CR3022 , IgG , monoclonal antibody , SARS-CoV-2

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School of Sciences and Humanities, Nazarbayev University, 53 Kabanbay Batyr Ave, Nur-Sultan, 010000, Kazakhstan
Centre for Life Sciences, National Laboratory Astana, Nazarbayev University, 53 Kabanbay Batyr Ave, Nur-Sultan, 010000, Kazakhstan
Michael G. DeGroote Institute for Infectious Disease Research, McMaster Immunology Research Centre, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, L8S 4L8, ON, Canada
Research Centre, Karaganda Medical University, 40 Gogol St, Karaganda, 100008, Kazakhstan
Faculty of Biological Sciences, Friedrich-Shiller-University Jena, Fürstengraben 1, Jena, 07743, Germany

School of Sciences and Humanities
Centre for Life Sciences
Michael G. DeGroote Institute for Infectious Disease Research
Research Centre
Faculty of Biological Sciences

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