Related Experiment Video
Updated: Dec 11, 2025
Engineering Chimeric Antigen Receptor-Natural Killer Cells Targeting Fungal Infections Using the Non-viral Sleeping Beauty Transposon System
Published on: October 4, 2024
Efficacy of Targeting SARS-CoV-2 by CAR-NK Cells
Abstract:
SARS-CoV-2, which causes COVID-19 disease, is one of greatest global pandemics in history. No effective treatment is currently available for severe COVID-19 disease. One strategy for implementing cell-based immunity involves the use of chimeric antigen receptor (CAR) technology. Unlike CAR T cells, which need to be developed using primary T cells derived from COVID-19 patients with lymphopenia, clinical success of CAR NK cell immunotherapy is possible through the development of allogeneic, universal, and 'off-the-shelf' CAR-NK cells from a third party, which will significantly broaden the application and reduce costs. Here, we develop a novel approach for the generation of CAR-NK cells for targeting SARS-CoV-2. CAR-NK cells were generated using the scFv domain of CR3022 (henceforth, CR3022-CAR-NK), a broadly neutralizing antibody for SARS-CoV-1 and SARS-CoV-2. CR3022-CAR-NK cells can specifically bind to RBD of SARS-CoV-2 and pseudotyped SARS-CoV-2 S protein, and can be activated by pseudotyped SARS-CoV-2-S viral particles in vitro. Further, CR3022-CAR-NK cells can specifically kill pseudo-SARS-CoV-2 infected target cells. Thus, 'off-the-shelf' CR3022-CAR-NK cells may have the potential to treat patients with severe COVID-19 disease.
Insights
Chimeric antigen receptor (CAR) NK cells targeting SARS-CoV-2 offer a potential treatment for severe COVID-19. These "off-the-shelf" cells show promise in preclinical studies for combating the pandemic virus.
Area of Science:
- Immunology
- Virology
- Biotechnology
Background:
- Severe COVID-19 disease lacks effective treatments, necessitating novel therapeutic strategies.
- Chimeric antigen receptor (CAR) technology offers a potential avenue for cell-based immunity.
- CAR NK cell immunotherapy presents advantages over CAR T cells, including allogeneic, 'off-the-shelf' availability.
Approach:
- Developed novel CAR-NK cells (CR3022-CAR-NK) targeting SARS-CoV-2 using the CR3022 antibody's scFv domain.
- Generated CAR-NK cells capable of binding the SARS-CoV-2 receptor-binding domain (RBD) and S protein.
- Demonstrated *in vitro* activation and specific killing of SARS-CoV-2-infected target cells by CR3022-CAR-NK cells.
Key Points:
- CR3022-CAR-NK cells specifically recognize and bind to SARS-CoV-2 RBD and pseudotyped S protein.
- These engineered NK cells are activated by SARS-CoV-2 S protein and effectively kill infected target cells *in vitro*.
- The study highlights the potential of allogeneic, universal CAR-NK cells for COVID-19 treatment.
Conclusions:
- 'Off-the-shelf' CR3022-CAR-NK cells represent a promising therapeutic strategy for severe COVID-19.
- This approach broadens the application and reduces costs associated with CAR-based immunotherapies.
- Further development of CAR-NK cell therapy could provide a vital tool against SARS-CoV-2 and future viral pandemics.
