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CAR Macrophages for SARS-CoV-2 Immunotherapy.
Wenyan Fu1,2,3, Changhai Lei1,2, Zetong Ma1
1Department of Biophysics, College of Basic Medical Sciences, Second Military Medical University, Shanghai, China.
Frontiers in Immunology
|August 9, 2021
Summary
Genetically engineered macrophages using chimeric antigen receptors (CARs) effectively clear SARS-CoV-2. CAR-MERTK macrophages offer a promising COVID-19 therapy by reducing viral load without causing inflammation.
Area of Science:
- Immunology
- Cellular and Molecular Medicine
- Infectious Diseases
Background:
- Targeted therapies for severe COVID-19 are limited.
- Macrophages are key immune cells in pathogen defense.
- Chimeric antigen receptors (CARs) can reprogram immune cells.
Purpose of the Study:
- To genetically engineer human macrophages with CARs to target SARS-CoV-2.
- To investigate the efficacy of different CAR constructs in clearing the virus.
- To evaluate the inflammatory response associated with CAR-modified macrophages.
Main Methods:
- Genetic engineering of human macrophages with CARs containing various intracellular domains (MERTK, MEGF10, FcRγ, CD3ζ).
- In vitro assessment of CAR-mediated phagocytosis, viral clearance, and cytokine expression.
- Comparison of CARMERTK efficacy against other CAR constructs.
Main Results:
- All tested CARs mediated SARS-CoV-2 clearance in vitro.
- CARMERTK macrophages reduced viral load without increasing pro-inflammatory cytokines.
- CARMERTK demonstrated an 'immunologically silent' scavenger effect.
Conclusions:
- CAR-engineered macrophages show potential for treating COVID-19.
- CARMERTK offers a novel therapeutic strategy for severe COVID-19, particularly in cases with hyperinflammation risk.
- Further research into CARs for COVID-19 treatment is warranted.
