한빛사논문
- 조회630
Da-Sol Kuen 1, Jihye Hong 2, Suyoung Lee 1, Choong-Hyun Koh 1, Minkyeong Kwak 1, Byung-Seok Kim 2, Mungyo Jung 3, Yoon-Joo Kim 4, Byung-Sik Cho 4, Byung-Soo Kim 3,5,6, Yeonseok Chung 1
1Laboratory of Immune Regulation, Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, 08826, Republic of Korea.
2Interdisciplinary Program for Bioengineering, Seoul National University, Seoul, 08826, Republic of Korea.
3School of Chemical and Biological Engineering, Seoul National University, Seoul, 08826, Republic of Korea.
4Department of Hematology, Catholic Hematology Hospital and Leukemia Research Institute, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea.
5Division of Life Sciences, College of Life Science and Bioengineering, Incheon National University, Incheon, 22012, Republic of Korea.
6Institute of Chemical Processes, Institute of Engineering Research, BioMAX, Seoul National University, Seoul, 08826, Republic of Korea.
CORRESPONDING AUTHORS : Byung-Sik Cho, Byung-Soo Kim, Yeonseok Chung
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, 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.
논문정보
- Research article
- 2023년 05월 (BRIC 등록일 2023-06-07)
- 국내 연구진
- 생명과학 > 면역학
댓글 작성 로그인
팝업 닫기관련 링크
관련분야 연구자보기
관련분야 논문보기
