A Personalized Cancer Vaccine that Induces Synergistic Innate and Adaptive Immune Responses
© 2023 Wiley-VCH GmbH.
| Publié dans: | Advanced materials (Deerfield Beach, Fla.). - 1998. - 35(2023), 36 vom: 30. Sept., Seite e2303080 |
|---|---|
| Auteur principal: | |
| Autres auteurs: | , , , , , , , , , |
| Format: | Article en ligne |
| Langue: | English |
| Publié: |
2023
|
| Accès à la collection: | Advanced materials (Deerfield Beach, Fla.) |
| Sujets: | Journal Article acute myeloid leukemia cytotoxic T cells extracellular nanovesicles iNKT cells memory immunity personalized vaccines Cancer Vaccines |
| Résumé: | © 2023 Wiley-VCH GmbH. 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 |
|---|---|
| Description: | Date Completed 08.09.2023 Date Revised 08.09.2023 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-4095 |
| DOI: | 10.1002/adma.202303080 |