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同种异体造血干细胞移植后针对感染病原体的免疫策略。

Strategies to harness immunity against infectious pathogens after haploidentical stem cell transplantation.

出版信息

Am J Transl Res. 2011;3(5):404-21. Epub 2011 Sep 10.

PMID:22046483
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3204893/
Abstract

Viral and fungal infections account for significant morbidity and mortality, particularly in pediatric patients with profound immune suppression resulting from allogeneic hematopoietic stem cell transplantation (HSCT). Therapies with anti-viral and anti-fungal drugs are often associated with significant toxicity, are of limited efficacy and can induce drug resistance. One innovative approach to prevent and/or treat viral and fungal infections involves the adoptive transfer of in vitro-expanded or in vitro-generated pathogen-specific T cells. This review summarizes the clinical trials that have been run to date with virus- and fungus-specific T cells, with special emphasis on the clinical context of haploidentical HSCT for pediatric malignancies. It will also discuss initiatives and strategies to overcome the hurdles associated with time-consuming and complex GMP-grade laboratory procedures required to generate pathogen-specific T cells.

摘要

病毒和真菌感染可导致严重的发病率和死亡率,尤其是在因异基因造血干细胞移植(HSCT)而导致深度免疫抑制的儿科患者中。抗病毒和抗真菌药物治疗通常与显著的毒性相关,疗效有限,并且可能诱导耐药性。一种预防和/或治疗病毒和真菌感染的创新方法涉及体外扩增或体外产生的病原体特异性 T 细胞的过继转移。本综述总结了迄今为止针对病毒和真菌特异性 T 细胞进行的临床试验,特别强调了同种异体 HSCT 治疗儿科恶性肿瘤的临床背景。它还将讨论克服与生成病原体特异性 T 细胞相关的耗时且复杂的 GMP 级实验室程序相关的障碍的举措和策略。

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本文引用的文献

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Selectively T cell-depleted allografts from HLA-matched sibling donors followed by low-dose posttransplantation immunosuppression to improve transplantation outcome in patients with hematologic malignancies.选择性清除 HLA 匹配的同胞供者移植物中的 T 细胞,然后给予低剂量的移植后免疫抑制,以改善血液系统恶性肿瘤患者的移植结果。
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Adoptive transfer and selective reconstitution of streptamer-selected cytomegalovirus-specific CD8+ T cells leads to virus clearance in patients after allogeneic peripheral blood stem cell transplantation.采用链霉亲和素选择的巨细胞病毒特异性 CD8+ T 细胞过继转移和选择性重建可导致异基因外周血造血干细胞移植后患者的病毒清除。
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