CAR T Cell Therapy: A Novel Approach to Combating Atherosclerosis

Engineered anti‑OxLDL CAR Tregs cut aortic plaque by ~70% in high‑cholesterol mice, suggesting a potential inflammation‑targeted strategy for residual atherosclerotic risk.

In a preclinical report, antigen‑specific CAR Tregs were deployed to suppress arterial inflammation and reduce plaque in mice genetically predisposed to high cholesterol. Treated animals showed roughly a 70% reduction in aortic plaque burden versus controls, a sizable effect in a relevant model that warrants careful translational follow-up.

The approach targets oxidized low‑density lipoprotein (OxLDL) within the plaque microenvironment. By engineering regulatory T cells with OxLDL‑directed CARs, investigators report local suppression of proinflammatory cytokines, reduced macrophage recruitment, and limited foam‑cell formation—mechanisms that plausibly explain the marked plaque reduction observed in vitro and in vivo.

In terms of the study details, atherosclerosis‑prone, high‑cholesterol mice received anti‑OxLDL CAR Tregs and were assessed at ~12 weeks. Plaque burden was the primary outcome; treated animals demonstrated the ~70% lower atherosclerotic plaque compared with untreated controls. The report notes small sample sizes and replication limited to a single animal model, so effect size should be interpreted in a preclinical context.

Translational hurdles remain before first‑in‑human testing. Key issues include antigen specificity and cross‑reactivity (to avoid off‑target binding), scalable GMP manufacturing of stable CAR Treg products, durability and arterial homing of transferred cells, characterization of on‑target/off‑tissue effects, and immunogenicity against the CAR or engineered cells.

Each item carries specific safety and feasibility implications and requires GLP‑compliant, stepwise evaluation—validated cross‑reactivity assays, extended dosing and toxicity studies, and demonstration of reproducible GMP production are priorities.

Key Takeaways:

• Anti‑OxLDL CAR Tregs reduced plaque by ~70% in a high‑cholesterol mouse model, indicating a pronounced preclinical effect.
• The mechanism centers on antigen‑specific Treg suppression of local inflammation and reduced macrophage recruitment within plaques.
• Major translational gaps remain: antigen cross‑reactivity assessment, GMP manufacturing, persistence and trafficking studies, and comprehensive safety profiling before human trials.