Controlling T-Cell Activation with Synthetic Dendritic Cells Using the Multivalency Effect
Publication year
2017Source
ACS Omega, 2, 3, (2017), pp. 937-945ISSN
Publication type
Article / Letter to editor

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Organization
Tumorimmunology
Biochemistry (UMC)
Molecular Materials
Journal title
ACS Omega
Volume
vol. 2
Issue
iss. 3
Page start
p. 937
Page end
p. 945
Subject
Molecular Materials; Radboudumc 2: Cancer development and immune defence RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 6: Metabolic Disorders RIMLS: Radboud Institute for Molecular Life SciencesAbstract
Artificial antigen-presenting cells (aAPCs) have recently gained a lot of attention. They efficiently activate T cells and serve as powerful replacements for dendritic cells in cancer immunotherapy. Focusing on a specific class of polymer-based aAPCs, so-called synthetic dendritic cells (sDCs), we have investigated the importance of multivalent binding on T-cell activation. Using antibody-functionalized sDCs, we have tested the influence of polymer length and antibody density. Increasing the multivalent character of the antibody-functionalized polymer lowered the effective concentration required for T-cell activation. This was evidenced for both early and late stages of activation. The most important effect observed was the significantly prolonged activation of the stimulated T cells, indicating that multivalent sDCs sustain T-cell signaling. Our results highlight the importance of multivalency for the design of aAPCs and will ultimately allow for better mimics of natural dendritic cells that can be used as vaccines in cancer treatment.
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