免疫系统
髓样
免疫疗法
医学
造血
抗原
骨髓
癌症研究
细胞因子
粒细胞巨噬细胞集落刺激因子
免疫学
生物
干细胞
遗传学
作者
Naseem Shah,Alexander J. Najibi,Ting‐Yu Shih,Angelo S. Mao,Azeem Sharda,David T. Scadden,David J. Mooney
标识
DOI:10.1038/s41551-019-0503-3
摘要
Acute myeloid leukaemia (AML) is a malignancy of haematopoietic origin that has limited therapeutic options. The standard-of-care cytoreductive chemotherapy depletes AML cells to induce remission, but is infrequently curative. An immunosuppressive AML microenvironment in the bone marrow and the paucity of suitable immunotherapy targets limit the induction of effective immune responses. Here, in mouse models of AML, we show that a macroporous-biomaterial vaccine that delivers the cytokine granulocyte–macrophage colony-stimulating factor (GM-CSF), the Toll-like-receptor-9 agonist cytosine–guanosine oligodeoxynucleotide and one or multiple leukaemia antigens (in the form of a defined peptide antigen, cell lysates or antigens sourced from AML cells recruited in vivo) induces local immune-cell infiltration and activated dendritic cells, evoking a potent anti-AML response. The biomaterial-based vaccine prevented the engraftment of AML cells when administered as a prophylactic and when combined with chemotherapy, and eradicated established AML even in the absence of a defined vaccine antigen. Biomaterial-based AML vaccination can induce potent immune responses, deplete AML cells and prevent disease relapse. A macroporous material encapsulating an immune-cell-activating cytokine, an adjuvant and tumour-associated antigens elicits prophylactic immunity to acute myeloid leukaemia in mice, and eradicates the disease when combined with chemotherapy.
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