A biomaterial-based vaccine eliciting durable tumour-specific responses against acute myeloid leukaemia.,Nature Biomedical Engineering

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A biomaterial-based vaccine eliciting durable tumour-specific responses against acute myeloid leukaemia.
Nature Biomedical Engineering ( IF 26.8 ) Pub Date : 2020-01-14 , DOI: 10.1038/s41551-019-0503-3
Nisarg J Shah _{1,

2,

3,

4,

5} , Alexander J Najibi _{1,

2} , Ting-Yu Shih _{1,

2} , Angelo S Mao _{1,

2} , Azeem Sharda _{3,

4} , David T Scadden _{3,

4,

6,

7} , David J Mooney _{1,

2}

Affiliation

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.

中文翻译：

一种基于生物材料的疫苗，可引发针对急性髓系白血病的持久肿瘤特异性反应。

急性髓系白血病 (AML) 是一种造血起源的恶性肿瘤，治疗选择有限。标准的细胞减灭化疗会消耗 AML 细胞以诱导缓解，但很少能治愈。骨髓中的免疫抑制性 AML 微环境和缺乏合适的免疫治疗靶点限制了有效免疫反应的诱导。在这里，在 AML 小鼠模型中，我们展示了一种大孔生物材料疫苗，可传递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（以特定的肽抗原、细胞裂解物或源自体内招募的 AML 细胞的抗原的形式）诱导局部免疫细胞浸润并激活树突状细胞，从而引发有效的抗 AML 反应。当作为预防剂施用以及与化疗结合使用时，基于生物材料的疫苗可以阻止 AML 细胞的植入，并且即使在没有确定的疫苗抗原的情况下也可以根除已建立的 AML。基于生物材料的 AML 疫苗接种可以诱导有效的免疫反应，消耗 AML 细胞并防止疾病复发。

更新日期：2020-01-14

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