造血
封锁
癌症研究
骨髓
干细胞
免疫系统
医学
归巢(生物学)
免疫检查点
髓样
髓性白血病
抗体
免疫疗法
趋化因子
免疫学
药理学
血小板
生物
内科学
受体
细胞生物学
生态学
作者
Quanyin Hu,Wujin Sun,Jinqiang Wang,Huitong Ruan,Xudong Zhang,Yanqi Ye,Song Shen,Chao Wang,Weiyue Lu,Ke Cheng,Gianpietro Dotti,Joshua F. Zeidner,Jun Wang,Zhen Gu
标识
DOI:10.1038/s41551-018-0310-2
摘要
Patients with acute myeloid leukaemia who relapse following therapy have few treatment options and face poor outcomes. Immune checkpoint inhibition, for example, by antibody-mediated programmed death-1 (PD-1) blockade, is a potent therapeutic modality that improves treatment outcomes in acute myeloid leukaemia. Here, we show that systemically delivered blood platelets decorated with anti-PD-1 antibodies (aPD-1) and conjugated to haematopoietic stem cells (HSCs) suppress the growth and recurrence of leukaemia in mice. Following intravenous injection into mice bearing leukaemia cells, the HSC-platelet-aPD-1 conjugate migrated to the bone marrow and locally released aPD-1, significantly enhancing anti-leukaemia immune responses, and increasing the number of active T cells, production of cytokines and chemokines, and survival time of the mice. This cellular conjugate also promoted resistance to re-challenge with leukaemia cells. Taking advantage of the homing capability of HSCs and in situ activation of platelets for the enhanced delivery of a checkpoint inhibitor, this cellular combination-mediated drug delivery strategy can significantly augment the therapeutic efficacy of checkpoint blockade.
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