Zusammenfassung
Invasive Pilzerkrankungen sind schwer zu behandeln und stellen eine erhebliche Bedrohung
für immungeschwächte Menschen dar. Die derzeitigen antimykotischen Wirkstoffe stoßen
an ihre Grenzen, einschließlich zunehmender Resistenzen gegen Antimykotika und unerwünschter
Wirkungen. Diese Übersicht soll einen umfassenden Überblick über neue Behandlungsstrategien
geben.
Abstract
Invasive fungal diseases (IFD) are difficult to treat and pose a significant threat
to immunocompromised individuals. Current antifungal agents face limitations, including
antifungal resistance and adverse effects. This review aims to give a comprehensive
overview of emerging treatment strategies.
Novel drugs in development are Ibrexafungerp, an orally available triterpenoid inhibiting
glucan synthesis, and Rezafungin representing the echinocandins with extended half-life
and improved tissue penetration, both recently licensed for certain indications. Fosmanogepix
targets glycosylphosphatidylinositol biosynthesis, while Olorofim, an orotomide, inhibits
fungal nucleic acid synthesis, both currently assessed in advanced clinical trials.
Immunotherapeutic approaches include immune checkpoint inhibitors to enhance immune
response in immunosuppressed individuals and fungal-specific allogeneic CAR-T cell
therapy. For prophylactic purpose in high-risk populations to develop IFD, monoclonal
antibodies against different virulence factors of Candida spp. have been discovered but are not yet seen in clinical trials. Vaccines against
distinct fungal antigens as well as pan fungal vaccines to prevent IFD are under development
in preclinical stages, notably for Candida spp., Cryptococcus spp., and Aspergillus spp., however, their clinical value is still discussed.
In summary, major advances to treat IFD have been observed, but challenges for their
establishment in the clinical routine persist.
Schlüsselwörter
invasive Pilzinfektion - Immuntherapie - monoklonale Antikörper - CAR-T-Zelltherapie
Keywords
invasive fungal diseases - immunotherapy - monoclonal antibodies - CAR-T cell therapy