诱导协同先天性和适应性免疫反应的个性化癌症疫苗

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, extracellular nanovesicles derived from alpha-galactosylceramide-conjugated autologous acute myeloid leukemia (AML) cells (ECNV-αGC) are presented 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 engages with and activates 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 serves as an antigen-presenting platform that can directly activate antigen-specific CD8 + T cells even in the absence of dendritic cells, thereby demonstrating a multifaceted cellular mechanism of immune activation.

Moreover, ECNV-αGC vaccination results in a significantly lower AML burden and higher percentage of leukemia-free survivors among cytarabine-treated hosts with AML. Human AML-derived ECNV-αGCs activate 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.