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Vaccine. 2004 Feb 17;22(7):865-71.

Recombinant antibodies: a natural partner in combinatorial antifungal therapy.

Author information

1
Medical Microbiology and NeuTec Pharma plc, 2nd Floor, Clinical Sciences Building 1, Central Manchester Healthcare Trust, Oxford Road, Manchester M13 9WL, UK.

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.

PMID:
15040939
DOI:
10.1016/j.vaccine.2003.11.032
[Indexed for MEDLINE]

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