Human recombinant antibody to HSP90: a natural partner in combination therapy.
Recent years have seen the development of the concept of combination therapy for treating severe fungal sepsis. The advantages of this approach are a potential improvement in patient survival and a reduction in the chance of resistance developing to each of the single agents. The disadvantage is that combining drugs may increase the chance of toxicity. Mycograb is a genetically recombinant antibody against fungal heat shock protein 90 (hsp90) which is poised to become the mainstay of combination therapy. This paper presents data on how hsp90 is important to fungi and what role it might play in human disease with possible interactions with interleukin 6 and nitric oxide. There is discussion of preclinical data demonstrating synergy in vitro between Mycograb and amphotericin B and caspofungin. The progress of Mycograb through a Phase II pharmacokinetic study when used in escalating doses with a liposomal amphotericin B preparation has also been reviewed. The concepts behind a Phase II pivotal study, where Mycograb or a placebo was given in combination with a liposomal amphotericin B drug for five days for the treatment of disseminated candidiasis are discussed.
Manchester University, Medical Microbiology, 2nd Floor, Clinical Sciences Building, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL, UK.
R C
RC
Matthews
J P
JP
Burnie
D000666:Amphotericin B / Q000627:therapeutic use; D000818:Animals; D000908:Antibodies, Fungal / Q000235:genetics* / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000627:therapeutic use; D002177:Candidiasis / Q000188:drug therapy / Q000628:therapy*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006360:Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D011994:Recombinant Proteins / Q000627:therapeutic use
D000908:Antibodies, Fungal; D000935:Antifungal Agents; D006360:Heat-Shock Proteins; D011994:Recombinant Proteins; D000666:Amphotericin B