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A Personalized Cancer Vaccine that Induces Synergistic Innate and Adaptive Immune Responses
Cited 2 time in
Web of Science
Cited 2 time in Scopus
- Authors
- Issue Date
- 2023-09
- Citation
- Advanced Materials, Vol.35 No.36
- Abstract
- 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-& alpha;GC) are presented as a personalized therapeutic vaccine that activates both innate and adaptive immune responses, bypassing the need to identify patient-specific neoantigens. ECNV-& alpha;GC 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-& alpha;GC 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-& alpha;GC 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-& alpha;GCs activate iNKT cells in both healthy individuals and patients with AML regardless of responsiveness to conventional therapies. Together, autologous AML-derived ECNV-& alpha;GCs may be a promising personalized therapeutic vaccine that efficiently establishes AML-specific long-term immunity without requiring the identification of neoantigens.
- ISSN
- 0935-9648
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