Journal
CHEMICAL SCIENCE
Volume 4, Issue 11, Pages 4168-4174Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c3sc51399h
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Funding
- Dutch Cancer Society [KUN2006-3699, KUN2009-4402]
- Dutch government [FES0908]
- European Research Council (ERC) [ERC-2010-AdG269019]
- Netherlands Organization for Scientific Research (NWO) [700.56.444, 700.58.430]
- Foundation for Fundamental Research on Matter (FOM) [10PR2791]
- NanoNext [7A.06, 3D.12]
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A new class of antibody-functionalized, semi-flexible and filamentous polymers (diameter 5-10 nm, length similar to 200 nm) with a controlled persistence length, a high degree of stereoregularity and the potential for multiple simultaneous receptor interactions has been developed. We have decorated these highly controlled, semi-stiff polymers with T cell activating anti-CD3 antibodies and analyzed their application potential as simple synthetic mimics of dendritic cells (sDCs). Our sDCs do not only activate T cells at significantly lower concentrations than free antibodies or rigid sphere-like counterparts (PLGA particles) but also induce a more robust T cell response. Our novel design further yields sDCs that are biocompatible and non-toxic. The observed increased efficacy highlights the importance of architectural flexibility and multivalency for modulating T cell response and cellular function in general.
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