To improve the efficacy of DC vaccination, Han et al. explored metabolic glycan labeling of DCs in vitro before adoptive transfer. DCs cultured with a sugar derivative containing azido groups upregulated CD86 and MHC-II, suggesting enhanced activation. Labeling improved antigen processing and presentation and subsequent priming of antigen-specific CD8+ T cells in vitro. In mouse models, transfer of labeled DCs increased antigen-specific CD8+ T cell priming, reduced tumor growth, and prolonged survival. Click conjugation of IL-15 to azido-DCs enhanced proliferation and stimulation of antigen-specific CD8+ T cells and further improved antitumor efficacy.
Contributed by Maartje Wouters
ABSTRACT: 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.