抗侵袭性真菌感染单克隆抗体研究进展

近20多年来,随着免疫缺陷患者的增多,侵袭性真菌感染发病率呈持续上升趋势,死亡率高居不下。现用的抗真菌药物主要有氮唑类、多烯类、棘白菌素类等,存在品种少、真菌耐药性增加和毒副作用大等问题,迫切需要研制新型抗真菌药物。单克隆抗体具有精准靶向的抗真菌作用,兼有调节机体免疫反应的功能,是治疗真菌感染的一种可行且具有独特优势的药物。从作用靶点分类,可以分为靶向真菌表面多糖、毒力因子、蛋白和跨界抗真菌单克隆抗体。从抗体来源分类又可以分为天然抗体和重组抗体。其作用机制包括直接抗真菌作用,即对毒素中和或对真菌的直接抑制作用;以及免疫增强作用,主要是补体的活化以驱动吞噬细胞清除或破坏致病真菌、中性粒细胞调理吞噬作用的激活以及诱导巨噬细胞调理吞噬。本文从药效学等方面总结了目前抗真菌感染单克隆抗体的研究进展,以及存在的问题。此外,针对抗真菌单克隆抗体的新型制备方法与传统制备方法进行了对比,并探讨了未来的发展方向。

Research progress of monoclonal antibodies against invasive fungal infections

In the past two decades, with the increase of immunodeficiency patients, the incidence of invasive fungal infections has been continuously rising, with high mortality rate. The currently used antifungal drugs mainly include azoles, polyenes, echinocandins, etc. The limited assortments result in increase of fungal drug resistance and toxic and side effects. There is an urgent need to develop new antifungal drugs. The monoclonal antibody has a precisely targeted anti-fungal effect and function of regulating the immune response, and therefore is feasible and unique for treating fungal infections. Based on functional target, it can be classified as polysaccharides, virulence factors, proteins and cross-boundary anti-fungal monoclonal antibodies that target fungal surfaces. Based on source of antibodies, it can be divided into natural antibodies and recombinant antibodies. Its mechanism includes directly antifungal effect that is direct neutralization of toxins or inhibition of fungal invasion, and immunopotentiation, mainly the activation of complement dependent cytotoxicity to clear or destroy pathogenic fungi and neutrophils to activate opsonophagocytosis and induce phagocytosis. This paper summarizes the current research progress of anti-fungal infection monoclonal antibodies’ pharmacodynamics and some existing problems. The comparison is made between new and traditional methods for preparation of anti-fungal monoclonal antibodies. The future development of this research field is discussed.