Targeted immunomodulation of dendritic cells (DCs) in vivo will enable manipulation of T-cell priming and amplification of anticancer immune responses, but a general strategy has been lacking. Here we show that DCs concentrated by a biomaterial can be metabolically labelled with azido groups in situ, which allows for their subsequent tracking and targeted modulation over time. Azido-labelled DCs were detected in lymph nodes for weeks, and could covalently capture dibenzocyclooctyne (DBCO)-bearing antigens and adjuvants via efficient Click chemistry for improved antigen-specific CD8+ T-cell responses and antitumour efficacy. We also show that azido labelling of DCs allowed for in vitro and in vivo conjugation of DBCO-modified cytokines, including DBCO–IL-15/IL-15Rα, to improve priming of antigen-specific CD8+ T cells. This DC labelling and targeted modulation technology provides an unprecedented strategy for manipulating DCs and regulating DC–T-cell interactions in vivo.
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All data supporting the results are provided with the manuscript. Raw datasets are available at https://dataverse.harvard.edu/privateurl.xhtml?token=4d292632-f627-4a56-8e01-60e36d0883f5.
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We acknowledge funding from the National Institutes of Health (grant nos. U01 CA214369 and R01 CA223255). H.W. gratefully acknowledges funding support from the Wyss Technology Development Fellowship. M.C.S. and C.M.T. acknowledge funding support from the Graduate Research Fellowship Program from the National Science Foundation. D.K.Y.Z. acknowledges support from the Canadian Institutes of Health Research. We thank A. J. Najibi at Harvard University for discussions.
D.J.M. conducts research sponsored by Novartis, Merck, Decibel and Amgen. D.J.M. consults for Agnovos and the Samyang Corporation. D.J.M. holds equity in Immulus. H.W. and D.J.M. are inventors of a patent application on the labelling technology.
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Wang, H., Sobral, M.C., Zhang, D.K.Y. et al. Metabolic labeling and targeted modulation of dendritic cells. Nat. Mater. (2020). https://doi.org/10.1038/s41563-020-0680-1