Recombinant antibodies: a natural partner in combinatorial antifungal therapy.
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.
Matthews
Ruth C
RC
Medical Microbiology and NeuTec Pharma plc, 2nd Floor, Clinical Sciences Building 1, Central Manchester Healthcare Trust, Oxford Road, Manchester M13 9WL, UK.
Burnie
James P
JP
D000818:Animals; D000908:Antibodies, Fungal / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D018841:HSP90 Heat-Shock Proteins / Q000502:physiology; D006801:Humans; D007167:Immunotherapy; D009181:Mycoses / Q000188:drug therapy / Q000628:therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use
D000908:Antibodies, Fungal; D000935:Antifungal Agents; D018841:HSP90 Heat-Shock Proteins; D011994:Recombinant Proteins