A biomaterial-based vaccine eliciting durable tumour-specific responses against acute myeloid leukaemia
A biomaterial-based vaccine eliciting durable tumour-specific responses against acute myeloid leukaemia
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DOI：
10.1038/s41551-019-0503-3
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发表时间：
2020-01-14
影响因子：
28.1
通讯作者：
Mooney, David J.
中科院分区：
文献类型：
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作者：
Shah, Nisarg J.;Najibi, Alexander J.;Mooney, David J.
急性髓性白血病（AML）是一种造血来源的恶性肿瘤，治疗选择有限。标准治疗的细胞减灭性化疗消耗AML细胞以诱导缓解，但很少治愈。骨髓中的免疫抑制性AML微环境和缺乏合适的免疫治疗靶标限制了有效免疫应答的诱导。在这里，在AML小鼠模型中，我们表明，一种大孔生物材料疫苗，提供细胞因子粒细胞-巨噬细胞集落刺激因子（GM-CSF），Toll样受体-9激动剂胞嘧啶-鸟苷寡脱氧核苷酸和一种或多种白血病抗原，（以确定的肽抗原的形式，细胞裂解物或来源于体内募集的AML细胞的抗原）诱导局部免疫细胞浸润和活化树突细胞，引起有效的抗AML应答。基于生物材料的疫苗在作为预防剂施用时以及在与化疗组合时防止AML细胞的植入，并且即使在不存在确定的疫苗抗原的情况下也根除了已建立的AML。基于生物材料的AML疫苗可以诱导有效的免疫应答，清除AML细胞并预防疾病复发。一种包封免疫细胞活化细胞因子、佐剂和肿瘤相关抗原的大孔材料可以增强小鼠对急性髓性白血病的预防性免疫，并在与化疗联合使用时根除疾病。
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.