Matthews Ruth C, Burnie James P
Medical Microbiology and NeuTec Pharma plc, 2nd Floor, Clinical Sciences Building 1, Central Manchester Healthcare Trust, Oxford Road, Manchester M13 9WL, UK.
Vaccine. 2004 Feb 17;22(7):865-71. doi: 10.1016/j.vaccine.2003.11.032.
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.
由于缺乏安全有效的抗真菌药物组合，两性霉素B或其脂质体衍生物形式的单一疗法是侵袭性真菌感染的常用治疗方法。联合治疗不一定有益——可能存在相互拮抗或无作用、毒性增加或与同时使用的药物相互干扰。但是，一种耐受性良好、具有协同作用的联合治疗的益处将是巨大的——增强的疗效将改善临床结果，减少长期治疗的必要性，并防止出现抗真菌药物耐药性。抗真菌抗体将是抗真菌治疗联合方法中的天然伙伴。对接受两性霉素B治疗的侵袭性念珠菌病患者体内发生的抗体反应进行分析后发现，康复与针对免疫显性热休克蛋白90（hsp90）的抗体之间存在密切关联。分子伴侣hsp90对酵母的生存能力至关重要。Mycograb是一种针对hsp90的人重组抗体，在体外和体内均显示出内在抗真菌活性以及与两性霉素B的协同作用。它目前正在一项针对确诊为侵袭性念珠菌病且正在接受脂质体两性霉素B治疗的患者的跨国、双盲、安慰剂对照试验中接受研究。
