Monoclonal Antibody-Based Anti-Cryptococcosis Therapy

Cryptococcosis remains one of the most severe invasive fungal diseases worldwide, causing high morbidity and mortality, particularly among immunocompromised individuals. Despite the availability of antifungal drugs, current therapeutic regimens are limited by drug toxicity, prolonged treatment, antifungal resistance, biofilm-associated tolerance, and frequent disease relapse, highlighting the need for novel therapeutic approaches. Monoclonal antibodies (mAbs) have emerged as promising immunotherapeutic agents because of their ability to specifically target fungal components while modulating host immune responses. This review provides a comprehensive overview of recent advances in monoclonal antibody-based strategies against Cryptococcus spp. Additionally, recent innovations in antibody engineering, including radioimmunotherapy, Fc engineering, nanobody technology, immune checkpoint modulation, and chimeric antigen receptor-(CAR)-based cellular therapies, are highlighted as emerging approaches with the potential to enhance antifungal efficacy and overcome current therapeutic limitations. Finally, we discuss the major challenges associated with the clinical translation of antifungal mAbs, including pharmacokinetic barriers, production costs, limited clinical evidence, and regulatory constraints. Collectively, the available evidence supports mAbs as promising adjunctive immunotherapeutic agents and underscores the importance of continued advances in antibody engineering and clinical research to facilitate their incorporation into future strategies for the treatment of cryptococcosis.