Abstract
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.
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All data supporting the results of this study are provided with the in the Article and its Supplementary Information. Raw datasets are available at https://doi.org/10.7910/DVN/44ARAC.
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Acknowledgements
We thank M. Brennan, A. Spielmann, M. Sobral, M. Dellacherie and H. Wang for technical assistance. The work was supported by the National Institutes of Health through grants R01CA223255, R01EB023287, U19HL129903 and U01CA214369. N.J.S. received support from the Cancer Research Institute through the CRI Irvington Postdoctoral Fellowship. A.J.N. acknowledges a Graduate Research Fellowship from the National Science Foundation.
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N.J.S., A.J.N., T.-Y.S., A.S.M., D.T.S. and D.J.M. designed the experiments. N.J.S., A.J.N., T.-Y.S., A.S.M. and A.S. conducted experiments and analysed data. N.J.S., A.J.N., D.T.S and D.J.M. wrote the manuscript.
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Magenta Therapeutics, director, equity and consulting: D.T.S.; Agios Pharmaceuticals, director, equity: D.T.S.; Fate Therapeutics, equity and consulting: D.T.S.; Clear Creek Bio, director, equity and consulting: D.T.S.; FOG Pharma, consulting: D.T.S.; Red Oak Medicines, director, equity and consulting: D.T.S.; Lifevaultbio, director, equity: D.T.S.; Bone Therapeutics, consulting: D.T.S.; Indee Labs, consulting: A.J.N.; Novartis, sponsored research: D.T.S and D.J.M.; Agnovos, consulting: D.J.M.; Amgen, sponsored research: D.J.M.; Samyang Corp., consulting: D.J.M.; Decibel, sponsored research: D.J.M.; Merck, sponsored research: D.J.M.; Immulus, equity: D.J.M.; Inventors, patent applications: N.J.S., A.J.N., A.S.M., T.-Y.S., D.J.M. and D.T.S.
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Shah, N.J., Najibi, A.J., Shih, TY. et al. A biomaterial-based vaccine eliciting durable tumour-specific responses against acute myeloid leukaemia. Nat Biomed Eng 4, 40–51 (2020). https://doi.org/10.1038/s41551-019-0503-3
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DOI: https://doi.org/10.1038/s41551-019-0503-3
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