Chimeric antigen receptor-engineered cell therapy for asthma: advances in targeting type 2 inflammation and...

Asthma is a heterogeneous chronic airway disease, and some patients remain inadequately controlled despite optimized inhaled therapy and targeted biologics. Chimeric antigen receptor (CAR)-engineered cells are being explored as a programmable approach to depleting pathogenic immune cells, regulating local inflammation, and potentially achieving durable disease control. This narrative review evaluates the biological rationale, therapeutic targets, cellular platforms, engineering strategies, evidence levels, and translational challenges of CAR-engineered cell therapy for asthma. Available studies have directed CAR-based recognition toward IL-5Rα-positive eosinophils and their progenitors, membrane IgE-positive cells, FcϵRIα-positive effector cells, disease-relevant allergens, and tissue-associated antigens. However, no asthma-directed CAR product has undergone clinical validation. Clinical translation will depend on overcoming the limited disease specificity imposed by target heterogeneity and expression on normal immune populations, while ensuring that engineered cells remain sufficiently controllable in terms of persistence, reversibility, and toxicity. These biological challenges must also be balanced against the practical demands of conditioning, manufacturing, cost, and appropriate patient selection. Translation should prioritize human target validation, clinically relevant chronic disease models, controllable CAR designs, and carefully selected patients with severe, biologic-refractory type 2-high asthma. CAR-engineered cells represent a promising experimental platform rather than an established alternative to current asthma therapy.