Promising immunotherapy against fungal diseases

ABSTRACT

Introduction: Despite the relatively high efficacy of antifungal drugs, invasive fungal infections (IFIs) are still associated with tremendous morbidity and mortality, since late diagnosis makes an antifungal drug therapy inefficient. Therefore, antifungal immunotherapies to specifically strengthen the host´s own immune mechanisms constitute an additional promising strategy in taking action against fungal pathogens.

Areas covered: The authors summarize efforts in research and clinical trials to provide safe and efficient immunotherapeutic options against invasive fungal diseases. Treatment of IFIs is challenging as the number of available antifungals is limited and further complications include: toxicity, drug interactions and the emergence of drug resistance. Susceptibility is determined by the impaired immune status of the host. Hence, augmenting immunity by immunotherapeutic interventions may offer future directions to treat IFI.

Expert opinion: A much better understanding of fungus and host cell interactions is essential for the development of safe and successful immunotherapeutic strategies. Indeed, there is encouraging preliminary data available that such approaches are possible; however, current data is too limited to allow solid conclusions on the risks and benefits in the clinical setting. Clinical trials focusing on the role of adjuvant immunotherapeutics with or without a combination of antifungals are highly needed for further evaluation.

KEYWORDS:

• Antifungal immunotherapy
• antifungal therapy
• innate and adaptive immunity
• vaccines

Article highlights

• The high numbers of patients undergoing hematopoetic stem cell transplantation, organ transplantation or suffering from various immunodeficiency lead to an increase of invasive fungal infections worldwide.

• Treatment with antifungal drugs such as polyenes, echinocandins and azoles represent the main standard of care.

• The number of available antifungal drugs is limited, and drugs differ from their spectrum of activity, route of administration, and bioavailability in target tissues. Further complications include toxicity, drug interactions and the emergence of drug resistance.

• Immunotherapy against fungal infections aims to activate cells of the innate as well as of the adaptive immune system by cytokine or chemokine administration.

• Other techniques support protection via granulocyte transfusion, adoptive T cell transfer, antibody administration or vaccination.

• Antibody administration and vaccination have shown very promising results, but more research in designing efficient and safe mAb for immunotherapies or in designing adjuvants is needed.

• Only a few clinical trials have been conducted so far; hence there is a need for additional studies to explore the potential of these immunotherapeutic strategies in the clinical setting.

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Declaration of interest

The authors have relevant affiliations or financial involvement with any organisation or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

W Posch, D Willfingseder and C Lass-Flörl are supported by the Austrian Science Fund (P24598 to DW, P25389 to WP and W1253-B24 doctoral program HOROS to CLF). The authors also supported by the CD Laboratory for Invasive Fungal Infections (CLF).