CAR-T therapy: Advances in respiratory diseases

Chimeric antigen receptor (CAR) T cell (CAR-T) therapy is a form of adoptive immunotherapy based on the genetic engineering of T lymphocytes. The expression of CARs on T cells facilitates precise, efficient immune responses by enabling direct binding to target cell-specific surface antigens, circumventing the need for major histocompatibility complex-restricted antigen presentation. Having achieved clinical success in treating refractory hematologic malignancies, research efforts have been increasingly directed toward expanding the application of CAR-T therapy, as there is growing interest in investigating its therapeutic potential for a range of respiratory diseases. This review systematically explores the expanding utilization of CAR-T therapy in treating respiratory diseases such as respiratory malignancies, severe asthma, infectious diseases, idiopathic pulmonary fibrosis, and autoimmune disorders with significant pulmonary involvement, providing a comprehensive summary of the current preclinical and clinical advancements. Despite encouraging outcomes, the clinical translation of CAR-T therapy for respiratory diseases is impeded by several persistent challenges, including the limited availability of tumor-specific antigens because of heterogeneous expression of target antigens, the impairment of CAR-T functionality by the immunosuppressive microenvironment of solid tumors, and considerable manufacturing and logistical hurdles. To address these obstacles, this review highlights emerging combinatorial strategies aimed at enhancing therapeutic efficacy and safety. With ongoing advancements, CAR-T therapy holds promise as a versatile and effective treatment, potentially achieving durable remissions and establishing a novel therapeutic paradigm for patients with otherwise refractory respiratory diseases.