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Dissertation/Thesis Abstract

Controlled delivery of a glutamate receptor modulator to promote regulatory T cells and restrain autoimmunity
by Gammon, Joshua Marvin, M.S., University of Maryland, College Park, 2015, 62; 10012602
Abstract (Summary)

Autoimmunity occurs when the immune system incorrectly recognizes and attacks self-molecules. Current therapies involve broad immunosuppressants that are not curative and leave patients immunocompromised. Dendritic cells (DCs) are a target for new therapies because DCs influence the differentiation of immune effector cells. N-Phenyl-7-(hydroxyimino)cyclopropa[ b]chromen-1a-carboxamide (PHCCC), a glutamate receptor enhancer, modulates DC cytokine profiles to polarize T cells toward regulatory phenotypes (TREG) that are protective in multiple sclerosis (MS). However, PHCCC treatment is limited by poor solubility, a short half-life, and toxicity. We hypothesized that controlled delivery of PHCCC from nanoparticles would alter DC function with reduced treatment frequency. PHCCC nanoparticles attenuated DC activation and promoted TREGs while reducing toxicity 30-fold. In mouse models of MS, these particles delayed disease and reduced severity compared to an equivalent dosing schedule of soluble drug. This outcome demonstrates controlled delivery of metabolic modulators can promote tolerance, suggesting a new route to improve autoimmune therapy.

Indexing (document details)
Advisor: Jewell, Christopher M.
Commitee: Muro, Silvia, Stroka, Kimberly
School: University of Maryland, College Park
Department: Bioengineering
School Location: United States -- Maryland
Source: MAI 55/03M(E), Masters Abstracts International
Subjects: Biomedical engineering, Immunology
Keywords: Autoimmunity, Biomaterial, Immunotherapy, Metabolism, Nanoparticle, Tolerance
Publication Number: 10012602
ISBN: 978-1-339-47588-2
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