[治疗侵袭性真菌疾病的创新疗法]。

Pub Date : 2024-04-24 DOI:10.1055/a-2132-9240
Sibylle C Mellinghoff, Oliver A Cornely, Parvin Mammadova, R. Sprute, Jannik Stemler
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引用次数: 0

摘要

侵袭性真菌病(IFD)难以治疗,对免疫力低下的人构成严重威胁。目前的抗真菌药物面临抗真菌耐药性和不良反应等限制。正在开发的新药有抑制葡聚糖合成的口服三萜类药物 Ibrexafungerp,以及代表棘白菌素类药物的 Rezafungin,它们的半衰期更长,组织穿透力更强,最近都获得了某些适应症的许可。Fosmanogepix 针对糖基磷脂酰肌醇的生物合成,而 Olorofim 是一种奥罗托酰胺,可抑制真菌核酸的合成,这两种药物目前都在高级临床试验中进行评估。免疫治疗方法包括免疫检查点抑制剂,可增强免疫抑制个体的免疫反应,以及真菌特异性异体 CAR-T 细胞疗法。为预防高危人群罹患 IFD,针对念珠菌属不同毒力因子的单克隆抗体已被发现,但尚未进入临床试验阶段。针对不同真菌抗原的疫苗以及预防 IFD 的泛真菌疫苗正在临床前开发阶段,特别是针对念珠菌属、隐球菌属和曲霉菌属的疫苗,但其临床价值仍有待讨论。
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[Innovative therapies for treatment of invasive fungal diseases].
Invasive fungal diseases (IFD) are difficult to treat and pose a significant threat to immunocompromised individuals. Current antifungal agents face limitations, including antifungal resistance and adverse effects. This review aims to give a comprehensive overview of emerging treatment strategies.Novel drugs in development are Ibrexafungerp, an orally available triterpenoid inhibiting glucan synthesis, and Rezafungin representing the echinocandins with extended half-life and improved tissue penetration, both recently licensed for certain indications. Fosmanogepix targets glycosylphosphatidylinositol biosynthesis, while Olorofim, an orotomide, inhibits fungal nucleic acid synthesis, both currently assessed in advanced clinical trials.Immunotherapeutic approaches include immune checkpoint inhibitors to enhance immune response in immunosuppressed individuals and fungal-specific allogeneic CAR-T cell therapy. For prophylactic purpose in high-risk populations to develop IFD, monoclonal antibodies against different virulence factors of Candida spp. have been discovered but are not yet seen in clinical trials. Vaccines against distinct fungal antigens as well as pan fungal vaccines to prevent IFD are under development in preclinical stages, notably for Candida spp., Cryptococcus spp., and Aspergillus spp., however, their clinical value is still discussed.In summary, major advances to treat IFD have been observed, but challenges for their establishment in the clinical routine persist.
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