Dissecting the biology of allogeneic HSCT to enhance the GvT effect whilst minimizing GvHD.
Dissecting the biology of allogeneic HSCT to enhance the GvT effect whilst minimizing GvHD.
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DOI：
10.1038/s41571-020-0356-4
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发表时间：
2020-08
期刊：
影响因子：
--
通讯作者：
Murphy WJ
中科院分区：
文献类型：
--
作者：
Blazar BR;Hill GR;Murphy WJ
同种异体造血干细胞移植（allo-HSCT）是第一个成功治疗血液系统恶性肿瘤患者的方法，主要是由于移植物抗肿瘤（GvT）的作用。为了将同种异体造血干细胞移植的适用范围扩大到老年患者和/或有合并症的患者，研究方法发生了巨大的变化，导致使用低强度调节方案，同时使用更积极的免疫抑制来更好地控制移植物抗宿主病（GvHD）。因此，疾病复发已成为同种异体造血干细胞移植后死亡的主要原因。因此，预防和治疗复发已成为最重要的，仍然是一个未满足的医疗需求。尽管有近60年的临床前和临床研究，但在不促进GvHD的情况下实现GvT效果所需的免疫学要求尚未完全确定。在此，我们回顾了与GvT效应相关的临床前模型和临床研究，重点关注复发机制和正在开发的免疫调节策略，以克服同种异体造血干细胞移植和自体造血干细胞移植后疾病复发。重点是讨论当前的知识和方法，这些知识和方法基于细胞疗法的使用，细胞因子增强免疫反应和双重用途抗体疗法或其他可以控制GvHD的药物，同时靶向癌细胞。造血干细胞移植（HSCT）是几种血液系统恶性肿瘤的潜在治疗方法。造血干细胞移植方法的改进大大降低了与治疗相关的发病率和死亡率，从而扩大了资格，并更加重视预防疾病复发。在这篇综述中，作者讨论了解剖HSCT生物学的方法，并利用生物学的见解来增强移植物抗肿瘤反应，特别是通过过继细胞治疗和其他免疫定向治疗，同时最大限度地减少移植物抗宿主病。
Allogeneic haematopoietic stem cell transplantation (allo-HSCT) was the first successful therapy for patients with haematological malignancies, predominantly owing to graft-versus-tumour (GvT) effects. Dramatic methodological changes, designed to expand eligibility for allo-HSCT to older patients and/or those with co-morbidities, have led to the use of reduced-intensity conditioning regimens, in parallel with more aggressive immunosuppression to better control graft-versus-host disease (GvHD). Consequently, disease relapse has become the major cause of death following allo-HSCT. Hence, the prevention and treatment of relapse has come to the forefront and remains an unmet medical need. Despite >60 years of preclinical and clinical studies, the immunological requirements necessary to achieve GvT effects without promoting GvHD have not been fully established. Herein, we review learnings from preclinical modelling and clinical studies relating to the GvT effect, focusing on mechanisms of relapse and on immunomodulatory strategies that are being developed to overcome disease recurrence after both allo-HSCT and autologous HSCT. Emphasis is placed on discussing current knowledge and approaches predicated on the use of cell therapies, cytokines to augment immune responses and dual-purpose antibody therapies or other pharmacological agents that can control GvHD whilst simultaneously targeting cancer cells. Haematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for several haematological malignancies. Improvements in HSCT methodologies have considerably reduced treatment-related morbidity and mortality, thus broadening eligibility and placing increased emphasis on the prevention of disease relapse. In this Review, the authors discuss approaches to dissecting the biology of HSCT and exploiting the biological insights to enhance the graft-versus-tumour response, in particular with adoptive cell therapies and other immune-directed therapies, whilst minimizing graft-versus-host disease.
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影响因子：
4
作者：
Bleakley, Marie;Riddell, Stanley R.
通讯作者：
Riddell, Stanley R.
影响因子：
20.3
作者：
Beelen, DW;Elmaagacli, A;Schaefer, UW
通讯作者：
Schaefer, UW
影响因子：
8
作者：
Alvarez, Maite;Simonetta, Federico;Negrin, Robert S.
通讯作者：
Negrin, Robert S.
DOI：
10.1038/nri3212
发表时间：
2012-05-11
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
16.8
作者：
Boudreau JE;Hsu KC
通讯作者：
Hsu KC