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巨细胞病毒的过继性T细胞免疫疗法

Adoptive T cell immunotherapy for cytomegalovirus.

作者信息

Peggs Karl S

机构信息

UCL Cancer Institute, Department of Haematology, Paul O'Gorman Building, 72 Huntley Street, London WC1E 6BT, UK.

出版信息

Expert Opin Biol Ther. 2009 Jun;9(6):725-36. doi: 10.1517/14712590902967588.

Abstract

Cytomegalovirus (CMV) is a major opportunistic pathogen following allogeneic transplantation, reflecting the inability of depressed host immunity to contain viral replication. Current antiviral drugs are limited by toxicities and lack of efficacy in established CMV disease, making adoptive immunotherapeutic strategies aimed at hastening virus-specific immune reconstitution attractive alternatives. A number of relatively small Phase I-II studies have demonstrated the feasibility of transferring CMV-specific T cells, varying in composition in terms of CD4+ and CD8+ T cell content. They have all suggested to varying degrees that restoration of CMV-specific immunity can be accelerated without an obvious effect on rates of graft-versus-host disease in those with CMV-seropositive donors. The majority also infer that recovery of laboratory measures of CMV-specific immunity correlate with clinical protection. Direct isolation of cells from donor blood now allows consideration of more widespread availability outside of a few academic centres, and equally importantly the delivery of randomised studies to establish the true efficacy of these strategies.

摘要

巨细胞病毒(CMV)是同种异体移植后一种主要的机会性病原体,这反映出宿主免疫功能低下无法抑制病毒复制。目前的抗病毒药物存在毒性限制,且对已确诊的CMV疾病疗效欠佳,这使得旨在加速病毒特异性免疫重建的过继性免疫治疗策略成为有吸引力的替代方案。一些规模相对较小的I-II期研究已证明,转移CMV特异性T细胞是可行的,这些T细胞在CD4+和CD8+ T细胞含量的组成上有所不同。这些研究均不同程度地表明,在CMV血清学阳性供体的患者中,恢复CMV特异性免疫可加速,且对移植物抗宿主病的发生率无明显影响。大多数研究还推断,CMV特异性免疫的实验室检测指标的恢复与临床保护相关。现在,从供体血液中直接分离细胞使得在少数几个学术中心之外更广泛地获取细胞成为可能,同样重要的是,开展随机研究以确定这些策略的真正疗效。

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