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Strategies of adoptive T -cell transfer to treat refractory viral infections post allogeneic stem cell transplantation.
异基因干细胞移植后过继 T 细胞转移治疗难治性病毒感染的策略。
Adoptive T cell transfer Refractory viral infections Virus-specific T cells
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摘要

BACKGROUND:Allogeneic hematopoietic stem cell transplantation (HSCT) can expose patients to a transient but marked immunosuppression, during which viral infections are an important cause of morbidity and mortality. Adoptive transfer of virus-specific T cells is an attractive approach to restore protective T -cell immunity in patients with refractory viral infections after allogeneic HSCT.
OBJECTIVES:This narrative review summarizes clinical evidence and developments of almost 30 years of adoptive T -cell transfer. The review is based on evidence extracted from PubMed searches and the clinical and experimental work of the authors.
CONTENT:Viral infections after HSCT are frequently caused by the endogenous reactivation of persistent pathogens such as cytomegalovirus (CMV), Epstein-Barr virus (EBV), and adenovirus (AdV). Current antiviral medication is not satisfactory and does not treat the underlying pathophysiology which is the lack of specific T -cell immunity. Adoptive transfer of virus-specific T cells could be a potentially curative, pathogen-specific, and non-toxic treatment providing long-term immunity against the virus. The isolation of virus-specific T cells from a healthy donor and infusion into a recipient is known as adoptive T -cell transfer and has been performed in many patients using different treatment protocols. Based on basic research, new isolation protocols aim at a safe and fast availability of cellular products for adoptive T -cell transfer. We summarize preclinical and clinical data on each of the main pathogens and on the technical approaches currently available to target either single antigens or even multiple pathogens.
CONCLUSION:Cellular therapy is considered as one of the major recent breakthroughs in medicine. Translation of this individualized treatment into first-line clinical routine is still limited. Main hurdles are availability of the technique, limited compatibility of classical phase III designs with cellular therapy, and regulatory restrictions. Multinational efforts are required to clarify the status of cellular treatment in first-line clinical routine with the overall objective to strengthen evidence-based treatment guidelines for the treatment of refractory viral infections post HSCT.

译文

背景: 异基因造血干细胞移植 (HSCT) 可以使患者遭受短暂但明显的免疫抑制,在此期间病毒感染是发病率和死亡率的重要原因。病毒特异性 T 细胞的过继转移是异基因 HSCT 后难治性病毒感染患者恢复保护性 T 细胞免疫的一种有吸引力的方法。
目的: 这篇叙述性综述总结了近 30 年过继性 T 细胞转移的临床证据和发展。该综述基于从 PubMed 检索中提取的证据以及作者的临床和实验工作。
内容: HSCT 后的病毒感染通常是由持续病原体如巨细胞病毒 (CMV) 、 eb病毒 (EBV) 和腺病毒 (AdV) 的内源性再激活引起的。目前的抗病毒药物并不令人满意,也不能治疗潜在的病理生理学,即缺乏特异性 T 细胞免疫。病毒特异性 T 细胞的过继转移可能是一种潜在的治疗性、病原体特异性和无毒的治疗方法,提供对病毒的长期免疫。从健康供体中分离病毒特异性 T 细胞并向受体输注被称为过继 T 细胞转移,并已在许多患者中使用不同的治疗方案进行。基于基础研究,新的隔离方案旨在为过继 T 细胞转移提供安全快速的细胞产品。我们总结了每种主要病原体的临床前和临床数据,以及目前可用于靶向单一抗原甚至多种病原体的技术方法。
结论: 细胞疗法被认为是医学近期的重大突破之一。这种个性化治疗转化为一线临床常规仍然有限。主要障碍是该技术的可用性、经典三期设计与细胞疗法的有限兼容性以及监管限制。需要多国努力阐明一线临床常规中的细胞治疗状况,总体目标是加强 HSCT 后难治性病毒感染治疗的循证治疗指南。

allogeneic stem cell transplantation

肿瘤 干细胞移植 治疗方法
概述  :  

干细胞移植是指在淋巴瘤、某些睾丸癌以及其他疾病治疗期间,医生使用健康的新的干细胞替代病态或无效的干细胞,或使用高剂量的一种治疗方法。需要移植的患者大体有以下几种原因:体内自身不能产生体内所需要的血细胞,因为其骨髓或血细胞呈现出一种病态且需要代替,或因为患者本身就有疾病,并接受了高剂量的化疗和/或放疗,与此同时破坏了癌细胞和干细胞。最常见的两种干细胞移植类型分别为自体移植和异基因移植。这两种干细胞移植是各类癌症治疗中比较常见的治疗方案,例如白血病、淋巴瘤和多发性骨髓瘤。异基因干细胞移植(All

Allogeneic   英 /,ælə(ʊ)dʒɪ'niːɪk; -dʒɪ'neɪɪk/   美 /,ælədʒɪ'niɪk/

       adj. 同种异体的;同种异系的

同根词   allogamous adj. [植] 异体受精的;[植] 异花受粉的;allogamy n. 异体受精,异花受粉;allograft n. [病理] 同种异体移植物

       Conclusions: Percutaneous injection of autologous bone marrow and allogeneic bone powder appears to be an effective and simple method for unicameral bone cysts. 结论:经皮注射自体骨髓加异体骨粉移植治疗单房性骨囊肿是一种简单、微创、疗效确切的方法。

 

Stem   英 /stem/  美 /stɛm/

       n. 干;茎;船首;血统;vt. 阻止;除去…的茎;给…装柄;vi. 阻止;起源于某事物;逆行

同根词   stemmed adj. 去掉茎或梗的;有茎或梗的;装有…柄的;stemless adj. 无茎的;无梗的;stemmer n. 抽梗机,除梗器;抽梗工人;stemmed v. 起源于(stem的过去分词形式);除去…的茎;给(假花等)装梗

       But the flow from the stem tip prevents them from doing this. 但是,来自主干顶端的(激素)流会阻止它们这么做。

 

Transplantation   英 /,trænsplɑːn'teɪʃən/

       n. 移植;迁移;移民

同根词   transplantable adj. 可移植的,可移种的;transplant n. 移植;移植器官;被移植物;移居者;transplanter n. 移植机;移植者;transplant vi. 移植;迁移;移居;transplant vt. 移植;迁移;使移居

       This involves transplantation of the organ from one person to another person, often to replace a non-functional organ in the latter. 它包括从一个个体到另一个个体的器官移植,往往是为了取代后者失去功能的某个器官。

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