异基因造血干细胞移植后白血病复发的控制：将移植与基...

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Control of leukemia relapse after allogeneic hematopoietic stem cell transplantation: integrating transplantation with genetically modified T cell therapies.


Leukemia relapse remains a significant cause of failure after allogeneic hematopoietic stem cell transplantation (HSCT). Although it is widely accepted that immunological components of the stem cell graft play a critical role in promoting leukemia eradication (graft versus leukemia effect), it is also evident that their efficacy is frequently inadequate and leukemia relapse still occurs. This article reviews recent insights into T cell-based posttransplant immunotherapy approaches aimed at preventing or controlling leukemia relapse. Donor lymphocyte infusion with T cells genetically modified with safety switches improves the patient's immune reconstitution while offering appropriate control of graft versus host disease. T lymphocytes engineered with artificial tumor-specific receptors such as αβ T-cell receptor chains or chimeric antigen receptors are major players in promoting antileukemia effects after allogeneic HSCT. The landscape of adoptive T cell therapies after allogeneic HSCT has seen significant achievements with the introduction of T cell engineering. Gene transfer grants the generation of T cell products characterized by standardizable specificity and functionality. This aspect is critical for scalable and reproducible approaches for application in large clinical studies. The clinical results so far reported are encouraging and multicenter studies conducted by pharmaceutical companies will provide definitive conclusions on the clinical impact of these new methodologies.


异基因造血干细胞移植后白血病复发的控制：将移植与基因修饰的细胞治疗相结合。

白血病的复发仍然是导致异基因造血干细胞移植之后导致失败的一个主要原因。虽然被广泛接受的理论是干细胞移植中的免疫组分中发挥了关键作用，促进白血病根除（移植物抗白血病效应），但是也很明显的是疗效经常不够好而且白血病复发仍然发生。本文综述了最近的T细胞移植后的免疫治疗的见解，旨在防治白血病复发。带有安全开关的基因修饰的供体淋巴细胞输注提高了患者的免疫重建，同时能够适当的控制移植物抗宿主病。人工肿瘤特异性受体如αβ T细胞受体链或者嵌合抗原受体修饰的T淋巴细胞是主要的在HSCT后起到抗白血病作用的参与者。转基因赋予了生产的T细胞能够有特异性和功能性。这是对于大量临床研究所必须的可扩展性和科重复性的关键。到目前的临床试验结果非常激动人心，由制药公司进行的多中心研究将就这些新方法对临床的影响提供明确的结论。
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