Recombinant antibodies: a natural partner in combinatorial antifungal therapy.

Abstract

Monotherapy, in the form of amphotericin B or one of its liposomal derivatives, is the usual treatment for invasive fungal infections, due to lack of a safe, effective combination of antifungal drugs. Combination therapy is not necessarily beneficial-there may be mutual antagonism or indifference, increased toxicity or interference with concomitant medication. But the benefits of a well-tolerated, synergistic combination would be great-the enhanced efficacy would improve clinical outcome, reduce the need for prolonged courses of treatment and prevent the emergence of antifungal drug resistance. Antifungal antibodies would be a natural partner in a combinatorial approach to antifungal therapy. Analysis of the antibody response which occurs in patients with invasive candidiasis, being treated with amphotericin B, showed a close correlation between recovery and antibody to the immunodominant heat shock protein 90 (hsp90). The molecular chaperone hsp90 is essential for yeast viability. Mycograb is a human recombinant antibody to hsp90 which shows intrinsic antifungal activity and synergy with amphotericin B both in vitro and in vivo. It is now the subject of a multinational, double-blind, placebo-controlled trial, in patients with culture-confirmed invasive candidiasis on liposomal amphotericin B.

• Authors: Ruth C Matthews, James P Burnie
• Journal: Vaccine (Vaccine) Vol. 22 Issue 7 Pg. 865-71 (Feb 17 2004) ISSN: 0264-410X [Print] Netherlands
• PMID: 15040939 (Publication Type: Journal Article, Review)

Chemical References

• Antibodies, Fungal
• Antifungal Agents
• HSP90 Heat-Shock Proteins
• Recombinant Proteins

Topics

• Animals
• Antibodies, Fungal (therapeutic use)
• Antifungal Agents (therapeutic use)
• Combined Modality Therapy
• HSP90 Heat-Shock Proteins (physiology)
• Humans
• Immunotherapy
• Mycoses (drug therapy, therapy)
• Recombinant Proteins (therapeutic use)