A new humanized antibody is effective against pathogenic fungi in vitro

Sci Rep. 2021 Sep 30;11(1):19500. doi: 10.1038/s41598-021-98659-5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Antibodies, Monoclonal, Humanized / genetics
  • Antibodies, Monoclonal, Humanized / isolation & purification
  • Antibodies, Monoclonal, Humanized / pharmacology*
  • Antibody Specificity / immunology
  • Chromatography, High Pressure Liquid
  • Dose-Response Relationship, Drug
  • Drug Resistance, Fungal / drug effects
  • Enzyme-Linked Immunosorbent Assay
  • Fungi / drug effects*
  • Genetic Engineering
  • Humans
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Light Chains / genetics
  • Mice
  • Microbial Sensitivity Tests
  • Phagocytosis
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / isolation & purification
  • Recombinant Fusion Proteins / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Antibodies, Monoclonal, Humanized
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Light Chains
  • Recombinant Fusion Proteins