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

Autor: Hui-Wen Chen, Chung-Yao Hsu, Jung Chen Lin, Zih Syun Fang, Gwo Harn M. Shiau, Ming Gu, Bing Yu Yao, Meiying Jung, Jeng Shiang Tsai, Che Ming Jack Hu, Jui Yi Chen, Tong Young Lee
Rok vydání: 2021
Předmět:
Cell Membrane Permeability
Materials science
Ultraviolet Rays
T-Lymphocytes
medicine.medical_treatment
Cell
Biocompatible Materials
02 engineering and technology
Lymphocyte Activation
010402 general chemistry
Immunotherapy
Adoptive
01 natural sciences
Polyethylene Glycols
Mice
chemistry.chemical_compound
Artificial antigen presenting cells
Cancer immunotherapy
Antigen
Biomimetic Materials
medicine
Animals
Humans
General Materials Science
Antigens
Antigen-presenting cell
Cell Proliferation
Mechanical Engineering
Hydrogels
Dendritic Cells
Neoplasms
Experimental
021001 nanoscience & nanotechnology
0104 chemical sciences
Cell biology
Mice
Inbred C57BL
medicine.anatomical_structure
chemistry
Mechanics of Materials
Self-healing hydrogels
Cytokines
Immunotherapy
0210 nano-technology
Ethylene glycol
Intracellular
Zdroj: Advanced Materials. 33:2101190
ISSN: 1521-4095
0935-9648
Popis: 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.
Databáze: OpenAIRE
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