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Passive Administration of Monoclonal Antibodies Against H. capsulatum and Others Fungal Pathogens
Published on: February 14, 2011
A new humanized antibody is effective against pathogenic fungi in vitro
Tomas Di Mambro1,2, Tania Vanzolini3, Pierpaolo Bruscolini4,5
1Department of Biomolecular Sciences, University of Urbino "Carlo Bo", 61029, Urbino, Italy. t.dimambro@diatheva.com.
Abstract:
Invasive fungal infections mainly affect patients undergoing transplantation, surgery, neoplastic disease, immunocompromised subjects and premature infants, and cause over 1.5 million deaths every year. The most common fungi isolated in invasive diseases are Candida spp., Cryptococcus spp., and Aspergillus spp. and even if four classes of antifungals are available (Azoles, Echinocandins, Polyenes and Pyrimidine analogues), the side effects of drugs and fungal acquired and innate resistance represent the major hurdles to be overcome. Monoclonal antibodies are powerful tools currently used as diagnostic and therapeutic agents in different clinical contexts but not yet developed for the treatment of invasive fungal infections. In this paper we report the development of the first humanized monoclonal antibody specific for β-1,3 glucans, a vital component of several pathogenic fungi. H5K1 has been tested on C. auris, one of the most urgent threats and resulted efficient both alone and in combination with Caspofungin and Amphotericin B showing an enhancement effect. Our results support further preclinical and clinical developments for the use of H5K1 in the treatment of patients in need.
Insights
A new humanized monoclonal antibody, H5K1, targets β-1,3 glucans in pathogenic fungi. It shows efficacy against Candida auris, alone and with existing antifungals, offering a potential new treatment for invasive fungal infections.
Area of Science:
- Mycology
- Immunology
- Infectious Diseases
Background:
- Invasive fungal infections cause over 1.5 million deaths annually, particularly in vulnerable patient groups.
- Current antifungal drugs face challenges due to side effects and emerging fungal resistance.
- Monoclonal antibodies are not yet established therapeutics for invasive fungal infections.
Purpose of the Study:
- To develop the first humanized monoclonal antibody targeting β-1,3 glucans, a key component of pathogenic fungi.
- To evaluate the efficacy of this novel antibody, H5K1, against *Candida auris*.
Main Methods:
- Development of a humanized monoclonal antibody (H5K1) specific for β-1,3 glucans.
- In vitro testing of H5K1 efficacy against *Candida auris*.
- Assessment of H5K1 in combination with established antifungals (Caspofungin, Amphotericin B).
Main Results:
- H5K1 demonstrated significant efficacy as a standalone treatment against *Candida auris*.
- Combination therapy with H5K1 and Caspofungin or Amphotericin B showed an enhanced therapeutic effect.
- The antibody specifically targets β-1,3 glucans, a crucial fungal cell wall component.
Conclusions:
- The developed monoclonal antibody H5K1 shows promise for treating invasive fungal infections.
- H5K1 represents a potential novel therapeutic strategy, particularly for difficult-to-treat fungi like *Candida auris*.
- Further preclinical and clinical studies are warranted to advance H5K1 for patient use.

