(573d) Immune Cell Homing Materials for Cancer Immunotherapy

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 macroporous hydrogel can be metabolically labeled with azido groups in situ, which allows for their subsequent tracking and targeted modulation over time. Azido-labeled 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 antitumor efficacy. We also show that azido-labeling 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 labeling and targeted modulation technology provides an unprecedented strategy to manipulate DCs and regulate DC-T cell interactions in vivo.