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基于单克隆抗体的系统性真菌感染免疫疗法

Immunotherapy against Systemic Fungal Infections Based on Monoclonal Antibodies.

作者信息

Boniche Camila, Rossi Suélen Andreia, Kischkel Brenda, Barbalho Filipe Vieira, Moura Ágata Nogueira D'Aurea, Nosanchuk Joshua D, Travassos Luiz R, Taborda Carlos Pelleschi

机构信息

Biomedical Sciences Institute, Department of Microbiology, University of São Paulo, Sao Paulo 05508-000, Brazil.

Tropical Medicine Institute, Department of Dermatology, Faculty of Medicine, University of Sao Paulo, Sao Paulo 05403-000, Brazil.

出版信息

J Fungi (Basel). 2020 Feb 29;6(1):31. doi: 10.3390/jof6010031.

Abstract

The increasing incidence in systemic fungal infections in humans has increased focus for the development of fungal vaccines and use of monoclonal antibodies. Invasive mycoses are generally difficult to treat, as most occur in vulnerable individuals, with compromised innate and adaptive immune responses. Mortality rates in the setting of our current antifungal drugs remain excessively high. Moreover, systemic mycoses require prolonged durations of antifungal treatment and side effects frequently occur, particularly drug-induced liver and/or kidney injury. The use of monoclonal antibodies with or without concomitant administration of antifungal drugs emerges as a potentially efficient treatment modality to improve outcomes and reduce chemotherapy toxicities. In this review, we focus on the use of monoclonal antibodies with experimental evidence on the reduction of fungal burden and prolongation of survival in in vivo disease models. Presently, there are no licensed monoclonal antibodies for use in the treatment of systemic mycoses, although the potential of such a vaccine is very high as indicated by the substantial promising results from several experimental models.

摘要

人类系统性真菌感染发病率的上升,增加了对真菌疫苗研发和单克隆抗体使用的关注。侵袭性真菌病通常难以治疗,因为大多数发生在免疫反应先天和适应性受损的易感个体中。在现有抗真菌药物治疗的情况下,死亡率仍然过高。此外,系统性真菌病需要长时间的抗真菌治疗,且副作用频繁发生,尤其是药物性肝损伤和/或肾损伤。使用单克隆抗体联合或不联合抗真菌药物,已成为一种潜在有效的治疗方式,可改善治疗效果并降低化疗毒性。在本综述中,我们重点关注在体内疾病模型中具有减少真菌负荷和延长生存期实验证据的单克隆抗体的使用。目前,尚无用于治疗系统性真菌病的获批单克隆抗体,不过,几个实验模型的大量 promising 结果表明,这种疫苗的潜力非常高。

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