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

Facile Transformation of Murine and Human Primary Dendritic Cells into Robust and Modular... 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Advanced Materials Wiley

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

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Publisher
Wiley
Copyright
© 2021 Wiley‐VCH GmbH
ISSN
0935-9648
eISSN
1521-4095
DOI
10.1002/adma.202101190
Publisher site
See Article on Publisher Site

Abstract

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.

Journal

Advanced MaterialsWiley

Published: Jul 1, 2021

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