Chimeric Antigen Receptor Regulatory T Cells Targeted Against Oxidized Low-Density Lipoprotein Reduce Atherosclerotic...

Area of Science:

• Immunology
• Cardiovascular Research
• Cell Therapy

Background:

• Atherosclerosis causes 18 million deaths annually, necessitating new therapies beyond LDL lowering.
• Oxidized LDL (OxLDL) drives inflammation and foam cell formation, key in atherosclerosis plaque development.
• Current treatments lack targeted anti-inflammatory approaches for atherosclerosis without systemic side effects.

Purpose of the Study:

• To develop and evaluate an anti-OxLDL specific chimeric antigen receptor T regulatory cell (CAR Treg) therapy.
• To assess the efficacy of CAR Tregs in mitigating inflammation and foam cell formation in vitro and in vivo.

Main Methods:

• Created an inducible Treg platform for anti-OxLDL CAR Treg generation.
• Evaluated immunosuppression and foam cell reduction in vitro.
• Tested murine anti-OxLDL CAR Tregs in hyperlipidemia and atherosclerosis mouse models.

Main Results:

• Anti-OxLDL CAR Tregs effectively reduced macrophage foam-cell formation in vitro.
• Significant inhibition of atherosclerotic plaque formation was observed in vivo.
• CAR Tregs demonstrated efficacy in immunocompetent mouse models.

Conclusions:

• Anti-OxLDL CAR Tregs mitigate inflammation and plaque deposition driven by OxLDL.
• This CAR Treg therapy represents a promising new therapeutic strategy for atherosclerosis.
• Targeting OxLDL with CAR Tregs offers a potential treatment for patients ineligible for current interventions.