Immunotherapy for Difficult-to-Treat Invasive Fungal Diseases

Opportunistic fungal diseases occur most ­commonly in highly immunocompromised patients, such as those with prolonged neutropenia or transplant recipients treated with ­intensive immunosuppression. Significant advances have been made in antifungal agents, which have led to improved therapeutic outcomes as well as a greater emphasis on antifungal prophylaxis targeted to the highly immunocompromised. In addition, we are gaining more knowledge about how our immune system recognizes fungi and protects us from fungal disease, while limiting potentially injurious inflammation and allergy. This knowledge has led to novel experimental approaches for immunotherapy. Progress in paving the way from promising preclinical approaches and limited clinical experience to properly conducted clinical trials has been poor – a reflection of invasive fungal diseases being relatively uncommon and the heterogeneity of the patient populations at risk, and insufficient funding for multicenter clinical immunotherapeutic trials. We describe our approaches to immunotherapy for severe and refractory invasive fungal diseases, realizing that important gaps in knowledge exist regarding benefit and toxicity. Future perspectives on immunotherapy are discussed.