aWestmead Institute for Medical Research at the University of Sydney bDepartment of Haematology, Westmead Hospital, Westmead cUniversity of Sydney, Camperdown, New South Wales, Australia.
Curr Opin Infect Dis. 2017 Dec;30(6):518-527. doi: 10.1097/QCO.0000000000000403.
Invasive fungal disease (IFD) is a cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant (HSCT) recipients. As more potent broad-spectrum antifungal agents are used in prophylaxis, drug resistance and less common fungal species have increased in frequency. Here we review current treatments available for IFD and examine the potential for adoptive T-cell treatment to enhance current therapeutic choices in IFD.
There is growing evidence supporting the role of T cells as well as phagocytes in antifungal immunity. T cells recognizing specific antigens expressed on fungal morphotypes have been identified and the role of T-cell transfer has been explored in animal models. The clinical efficacy of adoptive transfer of antigen-specific T cells for prophylaxis and treatment of viral infections post-HSCT has raised interest in developing good manufacturing practice (GMP)-compliant methods for manufacturing and testing fungus-specific T cells after HSCT.
As the outcomes of IFD post-HSCT are poor, reconstitution of antifungal immunity offers a way to correct the underlying deficiency that has caused the infection rather than simply pharmacologically suppress fungal growth. The clinical development of fungus specific T cells is in its early stages and clinical trials are needed in order to evaluate safety and efficacy.
侵袭性真菌病(IFD)是异基因造血干细胞移植(HSCT)受者发病率和死亡率的原因。随着更有效的广谱抗真菌药物在预防中使用,耐药性和较少见的真菌种类的频率增加。在这里,我们回顾了目前可用于 IFD 的治疗方法,并研究了过继 T 细胞治疗增强 IFD 目前治疗选择的潜力。
越来越多的证据支持 T 细胞以及吞噬细胞在抗真菌免疫中的作用。已经鉴定出识别真菌形态上特异性抗原的 T 细胞,并且已经在动物模型中探索了 T 细胞转移的作用。HSCT 后用于预防和治疗病毒感染的抗原特异性 T 细胞过继转移的临床疗效引起了人们对开发符合良好生产规范(GMP)的方法的兴趣,以便在 HSCT 后制造和测试真菌特异性 T 细胞。
由于 HSCT 后 IFD 的结果不佳,重建抗真菌免疫提供了一种纠正导致感染的潜在缺陷的方法,而不是简单地通过药理学抑制真菌生长。真菌特异性 T 细胞的临床开发仍处于早期阶段,需要进行临床试验以评估安全性和疗效。