Chimeric antigen receptor macrophage (CAR-M) immunotherapy in autoimmune inflammatory rheumatic diseases.

Chronic autoimmune inflammatory rheumatic diseases (AIRD), such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), juvenile idiopathic arthritis, systemic sclerosis (SSc), psoriatic arthritis (PsA), and ankylosing spondylitis (AS), are characterized by the dysregulation of the immune system and that of the neuroendocrine immune networks, leading to chronic inflammation and tissue damage. Perturbations of T, B, and macrophage cells result in uncontrolled inflammation. Traditional therapeutic approaches have focused on immunosuppressive drugs but more recently the use of biologics targeting specific cytokines or receptors on immune cells, and intracellular JAK pathways has been employed. However, these therapies often have limited efficacy and significant side effects. Moreover, they are not globally accessible due to high drug costs especially in poor as well as low- to middle-income countries. Cell immunotherapy, such as CAR-T and CAR-M cell therapy based on chimeric antigen receptor (CAR) technology, is opening up novel potential avenues for a precision approach to managing AIRD. This area is still experimental and in the research phase. This paper reviews the potential of CAR-M immunotherapy in AIRDs, highlighting its mechanisms of action and therapeutic applications.