CAR-macrophage immunotherapy targeting fibroblast-like synoviocytes ameliorates inflammatory and degenerative arthritis

IL-4–armored, FLS-targeted CAR-macrophages (CAR-M2-FAP and CAR-M2-NCL) attenuate arthritis severity in mouse RA and reduce synovitis, cartilage degeneration, and osteophytes in mouse OA.

• Why it matters: Pathogenic fibroblast-like synoviocytes drive synovial hyperplasia, persistent inflammation, and cartilage destruction in both rheumatoid arthritis and osteoarthritis, creating a shared therapeutic target despite different etiologies.
• What they did: The study engineered CAR-M2-FAP and CAR-M2-NCL to target FAP or nucleolin on pathological FLS, then tested enhanced FLS phagocytosis and an M2-like transcriptional profile in vitro and in mouse RA and OA models.
• The result: In both RA and OA mice, CAR-M2-FAP and CAR-M2-NCL reduced arthritis severity, synovial hyperplasia, cartilage loss, and bone erosion, and also lowered synovitis, cartilage degeneration, and osteophyte formation without overt acute toxicity.