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移植后感染的过继细胞疗法。

Adoptive cell therapies for posttransplant infections.

机构信息

Department of Haematology, Westmead Hospital.

Westmead Institute for Medical Research, The University of Sydney.

出版信息

Curr Opin Oncol. 2019 Nov;31(6):574-590. doi: 10.1097/CCO.0000000000000580.

Abstract

PURPOSE OF REVIEW

Viral and fungal infections cause significant morbidity and mortality following hematopoietic stem-cell transplantation (HSCT), primarily due to the prolonged and complex immunodeficient state that results from conditioning chemo-radiotherapy and subsequent prophylaxis of graft vs. host disease. Although currently available antimicrobial pharmacotherapies have demonstrated short-term efficacy, their toxicities often preclude long-term use, and cessation if frequently associated with recurrent infection. Adoptive cell therapy (ACT) offers the potential to more rapidly reconstitute antimicrobial immune responses in the posttransplant setting.

RECENT FINDINGS

Traditional approaches to manufacture of adoptive T-cell therapies are time consuming and limited to single pathogen specificity. Recent advances in the understanding of immunogenic epitopes, improved methods for pathogen-specific T-cell isolation and cultureware technologies is allowing for rapid generation of ACTs for clinical use.

SUMMARY

The current review summarizes the potential infectious targets and manufacturing methodologies for ACTs and contrasts their clinical efficacy and safety to currently available pharmacotherapies for patients recovering after HSCT.

摘要

目的综述

病毒和真菌感染是造血干细胞移植(HSCT)后导致发病率和死亡率显著增加的主要原因,这主要是由于预处理化疗和放疗导致的免疫缺陷状态延长和复杂化,以及随后移植物抗宿主病的预防。虽然目前可用的抗菌药物治疗已经证明了短期疗效,但它们的毒性往往排除了长期使用,并且如果经常停止使用,往往会导致反复感染。过继细胞治疗(ACT)有可能在移植后更迅速地重建抗菌免疫反应。

最近的发现

制造过继 T 细胞疗法的传统方法耗时且仅限于单一病原体特异性。对免疫原性表位的理解的最新进展,用于病原体特异性 T 细胞分离和培养箱技术的改进方法,使得 ACT 的快速生成可用于临床应用。

总结

目前的综述总结了 ACT 的潜在感染靶点和制造方法,并将其与 HSCT 后恢复患者的现有药物治疗的临床疗效和安全性进行了对比。

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