Dissecting the biology of allogeneic HSCT to enhance the GvT effect whilst minimizing GvHD.,Nature Reviews Clinical Oncology

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Dissecting the biology of allogeneic HSCT to enhance the GvT effect whilst minimizing GvHD.
Nature Reviews Clinical Oncology ( IF 81.1 ) Pub Date : 2020-04-20 , DOI: 10.1038/s41571-020-0356-4
Bruce R Blazar ₁ , Geoffrey R Hill ₂ , William J Murphy ₃

Affiliation

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 comorbidities, 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.

中文翻译：

解剖异基因 HSCT 的生物学以增强 GvT 效应，同时最大限度地减少 GvHD。

异基因造血干细胞移植 (allo-HSCT) 是血液系统恶性肿瘤患者的首个成功疗法，主要是由于移植物抗肿瘤 (GvT) 效应。旨在扩大同种异体造血干细胞移植适用于老年患者和/或合并症患者的巨大方法学变化导致使用强度降低的预处理方案，同时采用更积极的免疫抑制以更好地控制移植物抗宿主病。 GvHD）。因此，疾病复发已成为allo-HSCT后死亡的主要原因。因此，复发的预防和治疗已成为首要任务，仍然是未满足的医疗需求。尽管进行了超过 60 年的临床前和临床研究，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 效应相关的临床前建模和临床研究的经验，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的疾病复发。重点是讨论基于使用细胞疗法、细胞因子来增强免疫反应和双用途抗体疗法或其他可以控制 GvHD 同时靶向癌细胞的药理剂的当前知识和方法。专注于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的疾病复发。重点是讨论基于使用细胞疗法、细胞因子来增强免疫反应和双用途抗体疗法或其他可以控制 GvHD 同时靶向癌细胞的药理剂的当前知识和方法。专注于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的疾病复发。重点是讨论基于使用细胞疗法、细胞因子来增强免疫反应和双用途抗体疗法或其他可以控制 GvHD 同时靶向癌细胞的药理剂的当前知识和方法。

更新日期：2020-04-24

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