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Targeting inflammation with chimeric antigen receptor macrophages using a signal switch
Qi Cao1, Yiping Wang2, Jianwei Chen2
1Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, New South Wales, Australia. qi.cao@sydney.edu.au.
Nature Biomedical Engineering
|May 7, 2025
Summary
Engineered CAR macrophages (CAR-Ms) target inflammatory molecule TNF to reduce inflammation in acute and chronic diseases. This novel therapy shows promise for treating inflammatory conditions by reprogramming immune cells.
Area of Science:
- Immunology
- Cell Therapy
- Inflammatory Diseases
Background:
- Chimeric antigen receptor (CAR) T-cell therapy is successful in cancer treatment.
- CAR strategies offer potential for other clinical applications.
- Inflammatory diseases require new therapeutic approaches.
Purpose of the Study:
- To develop CAR macrophages (CAR-Ms) for treating inflammatory diseases.
- To program macrophages with an anti-inflammatory function.
- To evaluate CAR-M efficacy in preclinical models of inflammation.
Main Methods:
- Engineered CAR macrophages to recognize tumor necrosis factor (TNF).
- Activated an intracellular IL-4 signaling pathway for anti-inflammatory programming.
- Tested CAR-M therapy in mouse models of kidney ischemia-reperfusion injury and Adriamycin-induced nephropathy.
- Assessed CAR-M function in human cells.
Main Results:
- CAR-M therapy demonstrated efficacy in acute and chronic inflammatory disease models.
- CAR-Ms attenuated kidney ischemia-reperfusion injury by adopting an anti-inflammatory phenotype.
- CAR-Ms maintained anti-inflammatory function for weeks in chronic models, improving kidney outcomes.
- CAR-Ms reduced tissue injury in the liver and showed functional anti-inflammatory capacity in human cells.
Conclusions:
- CAR-M therapy, utilizing a signal-switching design, effectively treats inflammatory diseases.
- Engineered macrophages can be programmed for targeted anti-inflammatory functions.
- CAR-M therapy holds promise for a wide range of acute and chronic inflammatory conditions.
