除巨细胞病毒、EB病毒和腺病毒之外的病原体特异性T细胞。

Pathogen-Specific T Cells Beyond CMV, EBV and Adenovirus.

作者信息

Jiang Wei, Withers Barbara, Sutrave Gaurav, Clancy Leighton E, Yong Michelle I, Blyth Emily

机构信息

Faculty of Medicine and Health, The University of Sydney, Camperdown, Australia.

Westmead Institute of Medical Research, University of Sydney, Sydney, Australia.

出版信息

Curr Hematol Malig Rep. 2019 Aug;14(4):247-260. doi: 10.1007/s11899-019-00521-z.

Abstract

PURPOSE OF REVIEW

Infectious diseases contribute significantly to morbidity and mortality in recipients of allogeneic haematopoietic stem cell transplantation (aHSCT), particularly in the era of highly immunosuppressive transplant regimens and alternate donor transplants. Delayed cellular immune recovery is a major mechanism for the increased risk in these patients. Adoptive cell therapy with ex vivo manipulated pathogen-specific T cells (PSTs) is increasingly taking its place as a treatment strategy using donor-derived or third party-banked cells.

RECENT FINDINGS

The majority of clinical trial data in the form of early-phase studies has been in the prophylaxis or treatment of cytomegalovirus (CMV), Epstein-Barr virus (EBV) and adenovirus (AdV). Advancements in methods to select and enrich PSTs offer the opportunity to target the less common viral pathogens as well as fungi with this technology. Early clinical studies of PSTs targeting polyomaviruses (BK virus and JC virus), human herpesvirus 6 (HHV6), varicella zoster virus (VZV) and Aspergillus spp. have shown promising results in small numbers of patients. Other potential targets include herpes simplex virus (HSV), respiratory viruses and other invasive fungal species. In this review, we describe the burden of disease of this wider spectrum of pathogens, the progress in the development of manufacturing capability, early clinical results and the opportunities and challenges for implementation in the clinic.

摘要

综述目的

传染病在异基因造血干细胞移植(aHSCT)受者的发病和死亡中起重要作用,尤其是在高免疫抑制移植方案和替代供体移植的时代。细胞免疫恢复延迟是这些患者风险增加的主要机制。采用体外操作的病原体特异性T细胞(PSTs)进行过继性细胞治疗正日益成为一种使用供体来源或第三方储存细胞的治疗策略。

最新发现

以早期研究形式存在的大多数临床试验数据都用于预防或治疗巨细胞病毒(CMV)、爱泼斯坦-巴尔病毒(EBV)和腺病毒(AdV)。选择和富集PSTs方法的进展为利用该技术靶向较不常见的病毒病原体以及真菌提供了机会。针对多瘤病毒(BK病毒和JC病毒)、人疱疹病毒6型(HHV6)、水痘带状疱疹病毒(VZV)和曲霉属的PSTs的早期临床研究在少数患者中已显示出有前景的结果。其他潜在靶点包括单纯疱疹病毒(HSV)、呼吸道病毒和其他侵袭性真菌种类。在本综述中,我们描述了这类更广泛病原体的疾病负担、制造能力发展的进展、早期临床结果以及在临床中实施的机会和挑战。

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