A Personalized Cancer Vaccine that Induces Synergistic Innate and Adaptive Immune Responses

© 2023 Wiley-VCH GmbH.

Bibliographische Detailangaben
Veröffentlicht in:Advanced materials (Deerfield Beach, Fla.). - 1998. - 35(2023), 36 vom: 30. Sept., Seite e2303080
1. Verfasser: Kuen, Da-Sol (VerfasserIn)
Weitere Verfasser: Hong, Jihye, Lee, Suyoung, Koh, Choong-Hyun, Kwak, Minkyeong, Kim, Byung-Seok, Jung, Mungyo, Kim, Yoon-Joo, Cho, Byung-Sik, Kim, Byung-Soo, Chung, Yeonseok
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2023
Zugriff auf das übergeordnete Werk:Advanced materials (Deerfield Beach, Fla.)
Schlagworte:Journal Article acute myeloid leukemia cytotoxic T cells extracellular nanovesicles iNKT cells memory immunity personalized vaccines Cancer Vaccines
Beschreibung
Zusammenfassung:© 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
Beschreibung:Date Completed 08.09.2023
Date Revised 08.09.2023
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-4095
DOI:10.1002/adma.202303080