Chimeric antigen receptor-T cells: A novel immunotherapeutic strategy against invasive fungal infections.

Abstract

Invasive fungal diseases (IFDs) cause substantial global mortality, and current antifungal therapy is limited by resistance, toxicity, and narrow spectrum. Chimeric antigen receptor (CAR)-T cell therapy has achieved success in cancer treatment. Owing to major histocompatibility complex-independent antigen recognition, direct pathogen killing and the ability to enhance host immune responses, CAR-T cells are now being explored for infectious diseases, including IFDs, positioning them as a promising strategy for IFD therapy. Preclinical studies have shown activity against Aspergillus, Candida, Cryptococcus, and other pathogenic fungi. However, no antifungal CAR-T cell product has yet entered clinical trials, and the path to clinical translation remains unclear. Clinical translation faces challenges including manufacturing constraints, the limited number of antifungal CAR-T cell therapies, and safety risks. This review explores the potential and application challenges of CAR-T cells in the treatment of IFD, along with strategies to address these challenges, and proposes a framework for selecting antibody targets based on antigen conservation, surface accessibility, and validation status. It further analyzes the advantages of CAR-T cell therapy for IFD by comparing CAR-T cells with CAR-NK cells. These insights may contribute to the development of antifungal CAR-T cell therapy.