Metabolic labeling and targeted modulation of dendritic cells

Hua Wang, Miguel C. Sobral, David K.Y. Zhang, Adam N. Cartwright, Aileen Weiwei Li, Maxence O. Dellacherie, Christina M. Tringides, Sandeep T. Koshy, Kai W. Wucherpfennig, David J. Mooney

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1244-1252
Number of pages9
JournalNature Materials
Volume19
Issue number11
DOIs
StateAccepted/In press - 2020
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Mechanics of Materials
  • Mechanical Engineering

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