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.