Genetically recombinant antibodies: new therapeutics against candidiasis.
Historically, the therapy of serious fungal infection has been dominated by monotherapy with the polyene antibiotic amphotericin B. Clinical failures, side effects, the lack of alternatives and the toxicity of this drug have heightened the need to produce alternative therapies, which have included fluconazole, voriconazole and caspofungin. The observation that recovery from disseminated candidiasis was associated with an antibody response to the 47 kDa Candida heat-shock protein (HSP)90 homologue, coupled with the ability to sequence all the antibodies from patients who have recovered from the infection and to re-express the dominant ones as fragments in Escherichia coli, has opened the possibility of immunotherapy. The first recombinant antibody fragment, Mycograb (Neu Tec Pharma plc), against Candida HSP90 is now in clinical trials in patients with disseminated candidiasis in Europe and the US. Laboratory and early clinical data support the concept of synergy between Mycograb and amphotericin B. This should improve outcome and diminish the risk of resistance occurring to either drug, without an increase in toxicity, as this should be minimal in a human antibody fragment representing the natural antibody that a patient produces on recovery.
Burnie
James
J
University Department of Medical Microbiology, and NeuTec Pharma plc, 2nd floor, Clinical Sciences Building 1, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK. james.burnie@cmmc.nhs.uk
Matthews
Ruth
R
D000818:Animals; D000908:Antibodies, Fungal / Q000235:genetics* / Q000627:therapeutic use*; D000946:Antigens, Fungal / Q000737:chemistry / Q000276:immunology; D002177:Candidiasis / Q000628:therapy*; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000627:therapeutic use; D006801:Humans; D011994:Recombinant Proteins / Q000235:genetics / Q000627:therapeutic use
D000908:Antibodies, Fungal; D000946:Antigens, Fungal; D000939:Epitopes; D018841:HSP90 Heat-Shock Proteins; D011994:Recombinant Proteins