A biomaterial-based vaccine eliciting durable tumour-specific responses against acute myeloid leukaemia

Nat Biomed Eng. 2020 Jan;4(1):40-51. doi: 10.1038/s41551-019-0503-3. Epub 2020 Jan 14.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Biocompatible Materials
  • Bone Marrow / drug effects
  • Bone Marrow / immunology
  • Cancer Vaccines / administration & dosage*
  • Disease Models, Animal
  • Drug Development
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / immunology
  • Mice, Inbred C57BL
  • Toll-Like Receptor 9 / agonists

Substances

  • Biocompatible Materials
  • Cancer Vaccines
  • Toll-Like Receptor 9
  • Granulocyte-Macrophage Colony-Stimulating Factor