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

Assem Ashimova, Askhat Myngbay, Sergey Yegorov, Baurzhan Negmetzhanov, Irina Kadyrova, Angelina Yershova, Ulpan Kart, Matthew S. Miller, Gonzalo Hortelano

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

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.

Original languageEnglish
Article number2042
JournalPharmaceutics
Volume14
Issue number10
DOIs
Publication statusPublished - Oct 2022

Funding

The study was funded by a Faculty Development Competitive Research Grant (COVID, #280720FD1902) and ORAU grant #SST2017033 to G.H. The Science Committee of the Ministry of Education and Science of the Republic of Kazakhstan grant #AP09260233 to I.K. Science Committee of the Ministry of Education and Science of the Republic of Kazakhstan grant #AP09260233 supported in part A.A.

Keywords

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

ASJC Scopus subject areas

  • Pharmaceutical Science

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