Shah, Nisarg J.Najibi, Alexander J.Shih, Ting-YuMao, Angelo S.Sharda, AzeemScadden, David T.Mooney, David2023-07-262020-01-14Shah, Nisarg J., Alexander J. Najibi, Ting-Yu Shih, Angelo S. Mao, Azeem Sharda, David T. Scadden, David Mooney. "A biomaterial-based vaccine eliciting durable tumour-specific responses against acute myeloid leukaemia." Nat Biomed Eng 4, no. 1 (2020): 40-51. DOI: 10.1038/s41551-019-0503-32157-846Xhttps://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37376616Acute myeloid leukemia (AML) is a malignancy of hematopoietic origin with limited therapeutic options. The standard-of-care cytoreductive chemotherapy depletes AML cells to induce remission, but is rarely curative. A highly immunosuppressive AML microenvironment in the bone marrow and a paucity of suitable cell surface immunotherapy targets on AML cells precludes the induction of an effective endogenous adaptive immune response, which contributes to disease relapse. To promote a robust and durable immune-response against AML, we developed a biomaterial-based vaccine which provided a sustained release of GM-CSF to concentrate dendritic cells (DCs), TLR agonist CpG-ODN and one or more leukemia antigens in the form of a peptide antigen, cell lysates or sourced from in vivo recruited AML cells. The vaccine induced local cell infiltration and activated DCs to evoke a potent anti-AML immune response. Prophylactic vaccination alone prevented the engraftment of AML cells. Combining chemotherapy and the biomaterial vaccine maximized efficacy to eradicate established disease, even without a defined vaccine antigen. The combination treatment depleted AML cells and generated durable long-term effector T cell responses, and immunized transplanted mice against AML. The results from this experimental mouse model of AML demonstrate the capacity of a biomaterial-based vaccination approach to induce a potent immune response to deplete AML and prevent relapse.en-USComputer Science ApplicationsBiomedical EngineeringMedicine (miscellaneous)BioengineeringBiotechnologyJournal Article2023-07-2610.1038/s41551-019-0503-3