June 26, 2013

Human Monoclonal Antibody-Based Therapy in the Treatment of Invasive Candidiasis

Clinical and Developmental Immunology
Volume 2013 (2013), Article ID 403121, 9 pages
http://dx.doi.org/10.1155/2013/403121
Review Article

Human Monoclonal Antibody-Based Therapy in the Treatment of Invasive Candidiasis

Institute of Microbiology, Università Cattolica del Sacro Cuore, Rome, Italy
Received 14 May 2013; Accepted 13 June 2013
Academic Editor: Roberto Burioni
Copyright © 2013 Francesca Bugli et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Invasive candidiasis (IC) represents the leading fungal infection of humans causing life-threatening disease in immunosuppressed and neutropenic individuals including also the intensive care unit patients. Despite progress in recent years in drugs development for the treatment of IC, morbidity and mortality rates still remain very high. Historically, cell-mediated immunity and innate immunity are considered to be the most important lines of defense against candidiasis. Nevertheless recent evidence demonstrates that antibodies with defined specificities could act with different degrees showing protection against systemic and mucosal candidiasis. Mycograb is a human recombinant monoclonal antibody against heat shock protein 90 (Hsp90) that was revealed to have synergy when combined with fluconazole, caspofungin, and amphotericin B against a broad spectrum of Candida species. Furthermore, recent studies have established an important role for Hsp90 in mediating Candidaresistance to echinocandins, giving to this antibody molecule even more attractive biological properties. In response to the failure of marketing authorization by the CHMP (Committee for Medicinal Products for Human Use) a new formulation of Mycograb, named Mycograb C28Y variant, with an amino acid substitution was developed in recent years. First data on Mycograb C28Y variant indicate that this monoclonal antibody lacked efficacy in a murine candidiasis model.

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