[Innovative therapies for treatment of invasive fungal diseases].

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.
Competing Interests: SCM erhielt Forschungsförderung von der Universität zu Köln und vom Deutschen Zentrum für Infektionsforschung (DZIF) sowie von der DMykG; Vortragshonorare von Pfizer; Beratertätigkeit für Octapharma. RS erhielt Vortragshonorare von der Akademie für Infektionsmedizin e.V., Hikma und Pfizer sowie Reisekostenübernahme von Pfizer außerhalb der eingereichten Arbeit. JS erhielt Forschungsförderung vom Bundesministerium für Bildung und Forschung (BMBF), Basilea Pharmaceuticals, Noscendo; Vortragshonorare von AbbVie, Gilead, Hikma und Pfizer; Beratertätigkeit für Gilead, Alvea Vax. und Micron Research. OAC meldet Forschungsförderungen von BMBF, Cidara, EU-DG RTD (101037867), F2G, Gilead, MedPace, MSD, Mundipharma, Octapharma, Pfizer, Scynexis; Beratungshonorare und Honorare für Sachverständigengutachten von Abbvie, AiCuris, Biocon, Cidara, Gilead, IQVIA, Janssen, Matinas, MedPace, Menarini, Moderna, Molecular Partners, MSG-ERC, Noxxon, Octapharma, Pfizer, PSI, Scynexis, Seres; Referentenhonorare von Abbott, Abbvie, Al-Jazeera Pharmaceuticals/Hikma, Gilead, Grupo Biotoscana/United Medical/Knight, MedScape, MedUpdate, Merck/MSD, Noscendo, Pfizer, Shionogi, streamedup!; Teilnahme an einem DRC, DSMB oder Beratungsgremium für Boston Strategic Partners, Cidara, IQVIA, Janssen, MedPace, PSI, Pulmocide, Shionogi, The Prime Meridian Group; Ein Patent des German Patent and Trade Mark Office (DE 10 2021 113 007.7); Aktienanteile von CoRe Consulting, EasyRadiology; Andere Interessen von Wiley.
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