Improving macrophage responses to therapeutic antibodies by molecular engineering of SIRPα variants.

Improving macrophage responses to therapeutic antibodies by molecular engineering of SIRPα variants.
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DOI:
10.4161/onci.25773
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发表时间:
2013-09-01
期刊:
影响因子:
7.2
通讯作者:
Garcia KC
Garcia KC
中科院分区:
医学2区
文献类型:
--
作者:
Weiskopf K;Ring AM;Schnorr PJ;Volkmer JP;Volkmer AK;Weissman IL;Garcia KC

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CD47通过巨噬细胞表达的质膜受体信号调节蛋白α(SIRPα)转导抑制信号。许多癌症上调CD47以逃避免疫监视。我们最近设计了SIRPα变体,可有效拮抗CD47,用作抗癌免疫治疗剂。这些高亲和力SIRPα变体通过降低巨噬细胞介导的恶性细胞破坏的阈值与抗肿瘤抗体协同作用。
CD47 transduces inhibitory signals through signal-regulatory protein α (SIRPα), a plasma membrane receptor expressed by macrophages. Many cancers upregulate CD47 to evade immunosurveillance. We have recently engineered SIRPα variants that potently antagonize CD47 for use as anticancer immunotherapeutics. These high-affinity SIRPα variants synergize with antineoplastic antibodies by lowering the threshold for macrophage-mediated destruction of malignant cells.
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。
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