Hematopoietic stem cell transplantation in immunocompetent hosts without radiation or chemotherapy.
Hematopoietic stem cell transplantation in immunocompetent hosts without radiation or chemotherapy.
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DOI：
10.1126/scitranslmed.aae0501
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发表时间：
2016-08-10
影响因子：
17.1
通讯作者：
Shizuru JA
中科院分区：
文献类型：
--
作者：
Chhabra A;Ring AM;Weiskopf K;Schnorr PJ;Gordon S;Le AC;Kwon HS;Ring NG;Volkmer J;Ho PY;Tseng S;Weissman IL;Shizuru JA
造血干细胞（HSC）移植可以治疗多种血液系统疾病，包括恶性血液病、贫血和自身免疫性疾病。然而，患者必须接受毒性预处理方案，该方案使用化疗和/或放疗来消除宿主HSC并使供体HSC能够植入。先前的研究已经表明，抗c-Kit单克隆抗体从骨髓龛中耗尽HSC，允许供体HSC在免疫缺陷小鼠中植入。我们表明，宿主HSC清除依赖于Fc介导的抗体效应子功能，通过阻断CD 47（一种骨髓特异性免疫检查点）增强效应子活性，将抗c-Kit调节扩展到完全免疫活性的小鼠。联合治疗导致>99%的宿主HSC的消除和HSC移植后稳健的多谱系血液重建。这种仅使用生物制剂的靶向预处理方案有可能改变HSC移植的实践，并使其能够在更广泛的患者中使用。
Hematopoietic stem cell (HSC) transplantation can cure diverse diseases of the blood system, including hematologic malignancies, anemias, and autoimmune disorders. However, patients must undergo toxic conditioning regimens that use chemotherapy and/or radiation to eliminate host HSCs and enable donor HSC engraftment. Previous studies have shown that anti–c-Kit monoclonal antibodies deplete HSCs from bone marrow niches, allowing donor HSC engraftment in immunodeficient mice. We show that host HSC clearance is dependent on Fc-mediated antibody effector functions, and enhancing effector activity through blockade of CD47, a myeloid-specific immune checkpoint, extends anti–c-Kit conditioning to fully immunocompetent mice. The combined treatment leads to elimination of >99% of host HSCs and robust multilineage blood reconstitution after HSC transplantation. This targeted conditioning regimen that uses only biologic agents has the potential to transform the practice of HSC transplantation and enable its use in a wider spectrum of patients.
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影响因子：
3.7
作者：
Liu J;Wang L;Zhao F;Tseng S;Narayanan C;Shura L;Willingham S;Howard M;Prohaska S;Volkmer J;Chao M;Weissman IL;Majeti R
通讯作者：
Majeti R
CD47是人类急性髓样白血病干细胞的不良预后因素和治疗抗体靶标。
影响因子：
64.5
作者：
Majeti R;Chao MP;Alizadeh AA;Pang WW;Jaiswal S;Gibbs KD Jr;van Rooijen N;Weissman IL
通讯作者：
Weissman IL
影响因子：
4.8
作者：
Jiang, PH;Lagenaur, CF;Narayanan, V
通讯作者：
Narayanan, V
影响因子：
64.8
作者：
Chan, Charles K. F.;Chen, Ching-Cheng;Luppen, Cynthia A.;Kim, Jae-Beom;DeBoer, Anthony T.;Wei, Kevin;Helms, Jill A.;Kuo, Calvin J.;Kraft, Daniel L.;Weissman, Irving L.
通讯作者：
Weissman, Irving L.
影响因子：
4.8
作者：
Dvorak, C. C.;Gilman, A. L.;Cowan, M. J.
通讯作者：
Cowan, M. J.