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Blood:抗CD117抗体可同时清除正常的和异常的造血干细胞!

2019-03-16 不详 网络

中心点:抗CD117抗体可抑制并清除正常人HSCs。在MDS异种移植模型中,抗CD117抗体可清除人MDS细胞,促进正常人HSCs的移植。摘要:骨髓增生异常综合征(MDS)是一种克隆性疾病,可导致无效造血,并与转化成急性白血病的风险增加相关。MDS起源于造血干细胞(HSCs);因此,成功清除MDS HSCs是所有治疗方案的核心部分。但是,目前的治疗措施,包括异基因造血干细胞抑制(HCT),均不能消

中心点:

抗CD117抗体可抑制并清除正常人HSCs。

在MDS异种移植模型中,抗CD117抗体可清除人MDS细胞,促进正常人HSCs的移植。

摘要:

骨髓增生异常综合征(MDS)是一种克隆性疾病,可导致无效造血,并与转化成急性白血病的风险增加相关。MDS起源于造血干细胞(HSCs);因此,成功清除MDS HSCs是所有治疗方案的核心部分。

但是,目前的治疗措施,包括异基因造血干细胞抑制(HCT),均不能消除引发疾病的MDS HSCs,使得治愈可能性低、复发率高。在本研究中,研究人员发现结合细胞表面CD117(c-Kit)的单克隆抗体(mAbs)可靶向清除人HSCs。研究人员发现,抗人CD117 mAb,SR-1,在体外可抑制正常脐带血和骨髓的HSCs。而且,SR-1和临床级人源化的抗人CD117mAb,AMG191,在可清除正常的HSCs和MDS HSCs。抗CD117 mAb还可促进正常供体人HSCs在MDS移植小鼠模型中的移植,恢复正常的造血,并根除侵袭性病理性MDS细胞。

本研究首次证明了抗人CD117 mAbs可作为新的治疗方法来根除MDS HSCs,增强异基因HCT的治疗效果。除此之外,研究人员还为这些抗体制剂的应用奠定了基础,不仅可用于治疗MDS,还可用于治疗其他多种可采用移植治疗的HSC来源的血液免疫系统疾病。


原始出处:

Wendy W. Pang,et al.Anti-CD117 antibody depletes normal and myelodysplastic syndrome human hematopoietic stem cells in xenografted mice.Blood 2019 :blood-2018-06-858159; doi: https://doi.org/10.1182/blood-2018-06-858159 

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