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Steven Little

StevenĀ Little
Program
Beckman Young Investigators

Award Year
2008

Institution
University of Pittsburgh

Email:
srlittle@pitt.edu

Website:
http://www.engr.pitt.edu/bioengineering/main/people/faculty/little_steven.html

Research Title:
synthetic dendritic cells

Abstract:
Control over the induction of immunological tolerance would afford permanent allograft acceptance, bypassing a lifelong regimen of immunosuppressive agents. This tolerance is thought to be mediated by regulatory lymphocytes with powerful suppressive capacity. Our long term goal is to establish a therapeutically-relevant, modular platform capable of studying the effects of multiple soluble and surface-bound factors on the proliferation and suppressive capacity of regulatory T-cells in vivo. We demonstrate that biocompatible and degradable synthetic constructs (being the size of a cell) with covalently-bound monoclonal antibodies and encapsulated soluble cytokines/chemokines can strongly stimulate lymphocyte proliferation in vitro. Furthermore, we hypothesize that patterning the surface receptors (such that these particles would mimic a real immunological junction between a dendritic cell and T-cell) will further increase the stimulatory capacity of these "synthetic dendritic cells". In order to test this hypothesis, we present (for the first time) methods for precisely patterning 2 or more factors on the surface of a particle in a "bull's-eye" orientation.Control over the induction of immunological tolerance would afford permanent allograft acceptance, bypassing a lifelong regimen of immunosuppressive agents. This tolerance is thought to be mediated by regulatory lymphocytes with powerful suppressive capacity. Our long term goal is to establish a therapeutically-relevant, modular platform capable of studying the effects of multiple soluble and surface-bound factors on the proliferation and suppressive capacity of regulatory T-cells in vivo. We demonstrate that biocompatible and degradable synthetic constructs (being the size of a cell) with covalently-bound monoclonal antibodies and encapsulated soluble cytokines/chemokines can strongly stimulate lymphocyte proliferation in vitro. Furthermore, we hypothesize that patterning the surface receptors (such that these particles would mimic a real immunological junction between a dendritic cell and T-cell) will further increase the stimulatory capacity of these "synthetic dendritic cells". In order to test this hypothesis, we present (for the first time) methods for precisely patterning 2 or more factors on the surface of a particle in a "bull's-eye" orientation.

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