Facile Transformation of Murine and Human Primary Dendritic Cells into Robust and Modular Artificial Antigen‐Presenting Systems by Intracellular Hydrogelation

• Published in: Advanced materials (Weinheim) 2021-07, Vol.33 (30), p.e2101190-n/a
• Main Authors: Lin, Jung‐Chen, Hsu, Chung‐Yao, Chen, Jui‐Yi, Fang, Zih‐Syun, Chen, Hui‐Wen, Yao, Bing‐Yu, Shiau, Gwo Harn M., Tsai, Jeng‐Shiang, Gu, Ming, Jung, Meiying, Lee, Tong‐Young, Hu, Che‐Ming J.
• Format: Article
• Language: English
• Subjects: Animals; Anticancer properties; Antigens; Antigens - chemistry; artificial antigen‐presenting cells; Biocompatible Materials - chemistry; Biomedical materials; Biomimetic Materials - chemistry; cancer immunotherapy; Cell Membrane Permeability; Cell Proliferation; Cytokines; Cytokines - chemistry; Dendritic cells; Dendritic Cells - chemistry; Freezing; Humans; Hydrogels; Hydrogels - chemistry; Immunology; Immunotherapy; Immunotherapy, Adoptive; Interrogation; intracellular hydrogelation; Lymphocyte Activation; Lymphocytes; Materials science; Mice; Mice, Inbred C57BL; Modular construction; Modular systems; Morphology; Neoplasms, Experimental; Polyethylene glycol; Polyethylene Glycols - chemistry; radical polymerization; Robustness; Substrates; T-Lymphocytes; T‐cell expansion; Ultraviolet Rays
• ISSN: 0935-9648; 1521-4095
• DOI: 10.1002/adma.202101190

The growing enthusiasm for cancer immunotherapies and adoptive cell therapies has prompted increasing interest in biomaterials development mimicking natural antigen‐presenting cells (APCs) for T‐cell expansion. In contrast to conventional bottom‐up approaches aimed at layering synthetic substrates with T‐cell activation cues, transformation of live dendritic cells (DCs) into artificial APCs (aAPCs) is demonstrated herein using a facile and minimally disruptive hydrogelation technique. Through direct intracellular permeation of poly(ethylene glycol) diacrylate (PEG‐DA) hydrogel monomer and UV‐activated radical polymerization, intracellular hydrogelation is rapidly accomplished on DCs with minimal influence on cellular morphology and surface antigen display, yielding highly robust and modular cell–gel hybrid constructs amenable to peptide antigen exchange, storable by freezing and lyophilization, and functionalizable with cytokine‐releasing carriers for T‐cell modulation. The DC‐derived aAPCs are shown to induce prolonged T‐cell expansion and improve anticancer efficacy of adoptive T‐cell therapy in mice compared to nonexpanded control T cells, and the gelation technique is further demonstrated to stabilize primary DCs derived from human donors. The work presents a versatile approach for generating a new class of cell‐mimicking biomaterials and opens new venues for immunological interrogation and immunoengineering. An artificial antigen cell is prepared by directly transforming live dendritic cells into a cell–gel hybrid construct by photoactivated intracellular radical polymerization, enabling the preparation of a highly robust and modular cell‐mimicking biomaterial for immunoengineering. The gelated dendritic cells can be stored by lyophilization and effectively expand antigen‐specific T cells for anticancer adoptive cell therapy.