CAR-T-cell therapy for infectious diseases: from concept to clinic

Chimeric antigen receptor T-cell therapy is being extended from oncology to persistent and treatment-refractory infections. Translation requires recognition of pathogens or infected cells while preserving the function of organs already affected by infection and inflammation. This review critically evaluates target selection, receptor design, disease-specific evidence and translational constraints for CAR-T-cell therapy in infectious diseases. Three recognition classes have emerged: pathogen surface structures, infected-cell surface antigens and pathogen-derived peptide-HLA complexes. HIV provides the most mature clinical evidence, showing long-term persistence and reductions in reservoir-associated markers without reproducible antiretroviral therapy-free control. HBV, EBV and CMV studies support recognition of infected cells but expose risks related to hepatic injury, variable antigen expression and resistance of infected cells to lysis. Fungal CAR-T cells directed against β-glucan, hyphal antigens, glucuronoxylomannan or mannan have shown preclinical activity, whereas direct antibacterial CAR-T evidence remains minimal because bacterial clearance depends strongly on phagocytes and complement. Across pathogens, dynamic or soluble antigen, tissue reservoirs, impaired T-cell fitness, manufacturing delay and organ-specific inflammation constrain efficacy. Multispecific recognition, transient or switchable receptors, safety switches, local delivery, checkpoint modulation, cytokine-armored products and longitudinal blood-based monitoring may improve translation, but each requires infection-specific validation. Development should prioritize infections with stable target exposure, a treatment window compatible with cell delivery, measurable microbiological endpoints and a tolerable consequence of eliminating infected cells. Clinical progress will depend on matching the engineered effector mechanism to pathogen biology, tissue location and host immune status. Not applicable.