Shah and Najibi et al. developed a cryogel vaccine comprising biopolymer scaffolding, GM-CSF, the TLR9 agonist CpG-ODN, and tumor-associated antigens, and tested it in mice with acute myeloid leukemia (AML). Prophylactic vaccine containing either the WT1 antigen or AML cell lysate protected mice against WT1+ AML engraftment and rechallenge by inducing a tumor antigen-specific CTL response. In mice with established AML, combination of immunogenic cell death-inducing chemotherapy with cryogel vaccine (with or without antigen) eradicated AML and prevented relapse in 100% of treated mice, suggesting induction of a broad anti-AML CTL response.
Contributed by Anna Scherer
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.
Author Info: (1) John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. Wyss Institute for Biologically Inspired Engineering, Harvard University, Ca
Author Info: (1) John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA, USA. Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA. Harvard Stem Cell Institute, Cambridge, MA, USA. Department of Nanoengineering, Programs in Chemical Engineering and Immunology, University of California, San Diego, La Jolla, CA, USA. (2) John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA, USA. (3) John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA, USA. (4) John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA, USA. (5) Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA. Harvard Stem Cell Institute, Cambridge, MA, USA. (6) Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA. david_scadden@harvard.edu. Harvard Stem Cell Institute, Cambridge, MA, USA. david_scadden@harvard.edu. Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA. david_scadden@harvard.edu. Cancer Center, Massachusetts General Hospital, Boston, MA, USA. david_scadden@harvard.edu. (7) John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. mooneyd@seas.harvard.edu. Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA, USA. mooneyd@seas.harvard.edu.
