Abstract B053: In vivo metabolic labeling and targeted modulation of dendritic cells for enhanced cancer immunotherapy

Targeted immunomodulation of dendritic cells (DCs) is critical for optimizing antigen presentation processes and amplifying anticancer immune responses, but a general strategy has been lacking thus far. Here we show that the subcutaneously injected pore-forming alginate gels loaded with GM-CSF and azido-sugar nanoparticles can recruit and metabolically label DCs with azido groups in vivo, which allows for tracking and targeted modulation of DCs that migrate out of the gel scaffolds. Azido-labeled DCs were detected in both the gels and draining lymph nodes and enabled targeted delivery of dibenzocyclooctyne (DBCO)-bearing antigens and adjuvants via efficient Click chemistry, resulting in a higher level of antigen-specific CD8+ T-cells and better antitumor efficacy in comparison to unmodified antigens and adjuvants. We further show that azido-labeled DCs enable surface display of DBCO-cytokines, IL2 and IL15/IL15R for example, for targeted modulation of effector T-cells, which provides a general strategy to manipulate DCs and DC-T-cell interaction in vivo and opens a new avenue for developing enhanced cancer immunotherapy. Citation Format: Hua Wang, David J. Mooney. In vivo metabolic labeling and targeted modulation of dendritic cells for enhanced cancer immunotherapy [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B053.