In situ therapeutic vaccines for leukemia by chemo-nanoadjuvant therapy

Therapeutic vaccines introduce a potentially ultimate cure for cancers including leukemia. The personalized vaccines relying on neoantigens though exhibiting clinical benefits are afflicted by long and delicate manufacture procedure, high cost, and possibly incomplete coverage of heterogeneous tumor cells. Here, we report a facile strategy to generate potent in situ therapeutic vaccines, which effectively eliminate leukemia and induce long-term anti-leukemia immunity, by homoharringtonine-nano-dual-adjuvant (HHT-NDA) therapy. HHT effectively kills leukemia cells and generates abundant tumor antigens via inducing immunogenic cell death. NDAs cooperatively promote the maturation and antigen-presentation of dendritic cells by activating both nucleotide-binding oligomerization domain-containing protein 2 and toll-like receptor 9. The HHT-NDA treatment of murine MLL-AF9 acute myeloid leukemia model leads to 57-71 % complete regression and 100 % protection from rechallenge, in accordance with expansion of memory CD8⁺ T cells. This standard-of-care chemotherapy in tandem with nano-dual-adjuvant offers a novel strategy to generate in situ therapeutic vaccines for leukemia.