Acute myeloid leukemia (AML) is a hematopoietic malignancy with limited therapeutic options. Standard-of-care chemotherapy depletes AML cells to induce remission, but often precedes disease relapse. To promote robust and durable immunity against AML, we developed a macroporous cryogel-based vaccine which provided a sustained release of GM-CSF to concentrate dendritic cells (DCs), TLR agonist CpG-ODN, and leukemia antigen. Prophylactic vaccination in mice against AML cell lysates or peptide antigen induced a potent anti-tumor adaptive immune response and prevented the engraftment of AML cells. This immunity was transferable, as bone marrow transplanted from vaccinated mice immunized recipients against AML. In models of established disease, only the combination of chemotherapy and biomaterial vaccination entirely eradicated AML in all mice and generated long-term T cell immunity preventing relapse. Notably, in combination with chemotherapy, a cryogel vaccine delivering no antigen (only GM-CSF and CpG-ODN) generated robust AML-specific T cell immunity, depleted leukemia, and enabled long-term survival. In this setting, tumor antigens were likely sourced from chemotherapy-induced AML cell death, as AML cells expressing high levels of apoptotic markers were found in the vaccine site and draining lymph node, co-localizing with DCs activated by the vaccine. These results demonstrate the capacity of a biomaterial-based vaccine to induce a potent immune response depleting AML and preventing relapse, even without defined antigen targets.
Citation Format: Alexander J. Najibi, Nisarg J. Shah, Ting-Yu Shih, Angelo S Mao, Azeem Sharda, David T. Scadden, David J. Mooney. Cryogel-based cancer vaccine to treat acute myeloid leukemia [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2020 Oct 19-20. Philadelphia (PA): AACR; Cancer Immunol Res 2021;9(2 Suppl):Abstract nr PO085.