title: Controlling T-Cell Activation with Synthetic Dendritic Cells Using the Multivalency Effect.
abstract: 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.
authors.affiliation: Department of Molecular Materials, Institute for Molecules and Materials, Radboud University , Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands.
authors.forename: Roel
authors.initials: R
authors.lastname: Hammink
authors.affiliation: Department of Tumor Immunology and Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Radboud University , Geert Grooteplein 26, 6525 GA Nijmegen, The Netherlands.
authors.forename: Subhra
authors.initials: S
authors.lastname: Mandal
authors.affiliation: Department of Tumor Immunology and Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Radboud University , Geert Grooteplein 26, 6525 GA Nijmegen, The Netherlands.
authors.forename: Loek J
authors.initials: LJ
authors.lastname: Eggermont
authors.affiliation: Department of Tumor Immunology and Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Radboud University , Geert Grooteplein 26, 6525 GA Nijmegen, The Netherlands.
authors.forename: Marco
authors.initials: M
authors.lastname: Nooteboom
authors.affiliation: Department of Tumor Immunology and Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Radboud University , Geert Grooteplein 26, 6525 GA Nijmegen, The Netherlands.
authors.forename: Peter H G M
authors.initials: PH
authors.lastname: Willems
authors.affiliation: Department of Tumor Immunology and Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Radboud University , Geert Grooteplein 26, 6525 GA Nijmegen, The Netherlands.
authors.forename: Jurjen
authors.initials: J
authors.lastname: Tel
authors.affiliation: Department of Molecular Materials, Institute for Molecules and Materials, Radboud University , Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands.
authors.forename: Alan E
authors.initials: AE
authors.lastname: Rowan
authors.affiliation: Department of Tumor Immunology and Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Radboud University , Geert Grooteplein 26, 6525 GA Nijmegen, The Netherlands.
authors.forename: Carl G
authors.initials: CG
authors.lastname: Figdor
authors.affiliation: Department of Molecular Materials, Institute for Molecules and Materials, Radboud University , Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands.
authors.forename: Kerstin G
authors.initials: KG
authors.lastname: Blank