造血干细胞移植后病毒相关性疾病的 T 细胞治疗的挑战。
Challenges of T cell therapies for virus-associated diseases after hematopoietic stem cell transplantation.
机构信息
The Methodist Hospital, Texas Children's Hospital, Center for Cell and Gene Therapy, Baylor College of Medicine, 1102 Bates Street, Houston, TX 77030, USA.
出版信息
Expert Opin Biol Ther. 2010 Mar;10(3):337-51. doi: 10.1517/14712590903456003.
IMPORTANCE OF THE FIELD
Hematopoietic stem cell transplantation (HSCT) is the treatment of choice for many hematological malignancies and genetic disorders. The majority of patients do not have a human leukocyte antigen (HLA) identical sibling donor, and alternative stem cell sources include HLA-matched or mismatched unrelated donors and haploidentical related donors. However, alternative donor HSCT are associated with three major complications i) graft rejection; ii) graft-versus-host disease (GvHD); and iii) delayed immune reconstitution leading to viral infections and relapse.
AREAS COVERED IN THIS REVIEW
Graft rejection and the risk of GvHD can be significantly reduced by using intensive conditioning regimens, including in vivo T cell depletion as well as ex vivo T cell depletion of the graft. However, the benefits of removing alloreactive T cells from the graft are offset by the concomitant removal of T cells with anti-viral or anti-tumor activity as well as the profound delay in endogenous T cell recovery post-transplant. Thus, opportunistic infections, many of which are not amenable to conventional small-molecule therapeutics, are frequent in these patients and are associated with significant morbidity and high mortality rates. This review discusses current cell therapies to prevent or treat viral infections/reactivations post-transplant.
WHAT THE READER WILL GAIN
The reader will gain an understanding of the current state of cell therapy to prevent and treat viral infections post-HSCT, and will be introduced to preclinical studies designed to develop and validate new manufacturing procedures intended to improve therapeutic efficacy and reduce associated toxicities.
TAKE HOME MESSAGE
Reconstitution of HSCT recipients with antigen-specific T cells, produced either by allodepletion or in vitro reactivation, can offer an effective strategy to provide both immediate and long-term protection without harmful alloreactivity.
重要性领域
造血干细胞移植（HSCT）是许多血液恶性肿瘤和遗传疾病的首选治疗方法。大多数患者没有人类白细胞抗原（HLA）完全相同的兄弟姐妹供体，替代干细胞来源包括 HLA 匹配或不匹配的无关供体和单倍体相关供体。然而，替代供体 HSCT 与三个主要并发症有关：i）移植物排斥；ii）移植物抗宿主病（GvHD）；iii）免疫重建延迟导致病毒感染和复发。
本综述涵盖的领域
通过使用强化预处理方案，包括体内 T 细胞耗竭以及移植物的体外 T 细胞耗竭，可以显著降低移植物排斥和 GvHD 的风险。然而，从移植物中去除同种反应性 T 细胞的益处被同时去除具有抗病毒或抗肿瘤活性的 T 细胞以及移植后内源性 T 细胞恢复的深刻延迟所抵消。因此，机会性感染在这些患者中很常见，其中许多感染无法用传统的小分子治疗药物治疗，并且与显著的发病率和高死亡率相关。本文讨论了预防或治疗移植后病毒感染/再激活的当前细胞治疗方法。
读者将获得的收益
读者将了解预防和治疗 HSCT 后病毒感染的细胞治疗的现状，并将了解旨在开发和验证旨在提高治疗效果和降低相关毒性的新制造程序的临床前研究。
重要信息
用同种异体耗竭或体外再激活产生的抗原特异性 T 细胞重建 HSCT 受者，可以提供一种有效的策略，既能立即又能长期提供保护，而不会产生有害的同种异体反应性。
Zotero 插件