A personalized cancer vaccine that induces synergistic innate and adaptive immune responses.

To demonstrate potent efficacy, a cancer vaccine needs to activate both innate and adaptive immune cells. Personalized cancer vaccine strategies often require the identification of patient-specific neoantigens; however, the clonal and mutational heterogeneity of cancer cells presents inherent challenges. Here, we present extracellular nanovesicles derived from alpha-galactosylceramide-conjugated autologous acute myeloid leukemia (AML) cells (ECNV-αGC) as a personalized therapeutic vaccine that activates both innate and adaptive immune responses, bypassing the need to identify patient-specific neoantigens. ECNV-αGC vaccination directly engaged with and activated both invariant natural killer T (iNKT) cells and leukemia-specific CD8 + T cells in mice with AML, thereby promoting long-term anti-leukemic immune memory. ECNV-αGC sufficiently served as an antigen-presenting platform that could directly activate antigen-specific CD8 + T cells even in the absence of dendritic cells, thereby demonstrating a multi-faceted cellular mechanism of immune activation. Moreover, ECNV-αGC vaccination resulted in a significantly lower AML burden and higher percentage of leukemia-free survivors among cytarabine-treated hosts with AML. Human AML-derived ECNV-αGCs activated iNKT cells in both healthy individuals and patients with AML regardless of responsiveness to conventional therapies. Together, autologous AML-derived ECNV-αGCs may be a promising personalized therapeutic vaccine that efficiently establishes AML-specific long-term immunity without requiring the identification of neoantigens. This article is protected by copyright. All rights reserved.