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.
Highlights
C. auris is tolerant to high salt concentrations and to high temperatures (42 °C)[15]
C. auris can adhere to biotic and abiotic surfaces and colonize them for weeks and months becoming a very serious problem for the invasive devices used in the hospitals[13]
In this paper we reported the development and the characterization of a new humanized monoclonal antibody derived from monoclonal antibodies (mAbs) 2G8 and able to recognize β-1,3 glucans of pathogenic fungi such as Candida spp
Summary
Part of its danger comes from biofilm formation and from the production of phospholipases and p roteinases[16] This profile is probably not complete, but it does provide a reasonable explanation for 60% m ortality[13]. The action spectrum of antifungal agents should be balanced, not too limited and not too broad: effective against several species but not subject to early resistance They should be stable and have limited off-target interactions and a known pharmacokinetic. Monoclonal antibodies are promising therapeutic and diagnostic tools in different clinical contexts such as cancer, infective and autoimmune d iseases[19] Thanks to their high specificity for the determinant antigen, several mAbs were developed to treat fungal infections and reduce their bottlenecks but none of them reached the clinical trials because of their murine nature (with the exception of Mycograb[22,23])
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
