TY - JOUR
T1 - Metabolic glycan labeling immobilizes dendritic cell membrane and enhances antitumor efficacy of dendritic cell vaccine
AU - Han, Joonsu
AU - Bhatta, Rimsha
AU - Liu, Yusheng
AU - Bo, Yang
AU - Elosegui-Artola, Alberto
AU - Wang, Hua
N1 - The authors would like to acknowledge the financial support from NSF DMR 21-43673 CAR (H.W.), NIH R01CA274738 (H.W.), NIH R21CA270872 (H.W), and start-up package (H.W.) from the Department of Materials Science and Engineering at the University of Illinois at Urbana-Champaign and the Cancer Center at Illinois (CCIL). J.H. acknowledges the support from the Cancer Scholars for Translational and Applied Research (C*STAR) Program sponsored by the Cancer Center at Illinois and the Carle Cancer Center under Award Number CST EP012023. R.B. acknowledges the support from the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health under Award Number T32EB019944. We would also like to acknowledge the help from Alvaro Hernandez and Jenny Drnevich at UIUC Roy J. Carver Biotechnology Center on mRNA sequencing and transcriptome analysis. A.E.A. acknowledges the support from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement number 851055). A.E.A. is supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (CC2214), the UK Medical Research Council (CC2214), and the Wellcome Trust (CC2214).
PY - 2023/12
Y1 - 2023/12
N2 - Dendritic cell (DC) vaccine was among the first FDA-approved cancer immunotherapies, but has been limited by the modest cytotoxic T lymphocyte (CTL) response and therapeutic efficacy. Here we report a facile metabolic labeling approach that enables targeted modulation of adoptively transferred DCs for developing enhanced DC vaccines. We show that metabolic glycan labeling can reduce the membrane mobility of DCs, which activates DCs and improves the antigen presentation and subsequent T cell priming property of DCs. Metabolic glycan labeling itself can enhance the antitumor efficacy of DC vaccines. In addition, the cell-surface chemical tags (e.g., azido groups) introduced via metabolic glycan labeling also enable in vivo conjugation of cytokines onto adoptively transferred DCs, which further enhances CTL response and antitumor efficacy. Our DC labeling and targeting technology provides a strategy to improve the therapeutic efficacy of DC vaccines, with minimal interference upon the clinical manufacturing process.
AB - Dendritic cell (DC) vaccine was among the first FDA-approved cancer immunotherapies, but has been limited by the modest cytotoxic T lymphocyte (CTL) response and therapeutic efficacy. Here we report a facile metabolic labeling approach that enables targeted modulation of adoptively transferred DCs for developing enhanced DC vaccines. We show that metabolic glycan labeling can reduce the membrane mobility of DCs, which activates DCs and improves the antigen presentation and subsequent T cell priming property of DCs. Metabolic glycan labeling itself can enhance the antitumor efficacy of DC vaccines. In addition, the cell-surface chemical tags (e.g., azido groups) introduced via metabolic glycan labeling also enable in vivo conjugation of cytokines onto adoptively transferred DCs, which further enhances CTL response and antitumor efficacy. Our DC labeling and targeting technology provides a strategy to improve the therapeutic efficacy of DC vaccines, with minimal interference upon the clinical manufacturing process.
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U2 - 10.1038/s41467-023-40886-7
DO - 10.1038/s41467-023-40886-7
M3 - Article
C2 - 37598185
AN - SCOPUS:85168362365
SN - 2041-1723
VL - 14
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 5049
ER -