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|a dc
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|a Maldonado, Roberto A.
|e author
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|a Massachusetts Institute of Technology. Department of Chemical Engineering
|e contributor
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|a Koch Institute for Integrative Cancer Research at MIT
|e contributor
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|a Langer, Robert
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|a LaMothe, Robert A.
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|a Ferrari, Joseph D.
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|a Zhang, Ai-Hong
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|a Rossi, Robert J.
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|a Kolte, Pallavi N.
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|a Griset, Aaron P.
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|a O'Neil, Conlin P.
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|a Altreuter, David H.
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|a Browning, Erica A.
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|a Johnston, Lloyd P. M.
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|a Farokhzad, Omid C.
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|a Scott, David W.
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|a von Andrian, Ulrich H.
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|a Kishimoto, Takashi Kei
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|a Langer, Robert S
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|a Polymeric synthetic nanoparticles for the induction of antigen-specific immunological tolerance
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|b National Academy of Sciences (U.S.),
|c 2015-06-30T16:37:56Z.
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|z Get fulltext
|u http://hdl.handle.net/1721.1/97585
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|a Current treatments to control pathological or unwanted immune responses often use broadly immunosuppressive drugs. New approaches to induce antigen-specific immunological tolerance that control both cellular and humoral immune responses are desirable. Here we describe the use of synthetic, biodegradable nanoparticles carrying either protein or peptide antigens and a tolerogenic immunomodulator, rapamycin, to induce durable and antigen-specific immune tolerance, even in the presence of potent Toll-like receptor agonists. Treatment with tolerogenic nanoparticles results in the inhibition of CD4+ and CD8+ T-cell activation, an increase in regulatory cells, durable B-cell tolerance resistant to multiple immunogenic challenges, and the inhibition of antigen-specific hypersensitivity reactions, relapsing experimental autoimmune encephalomyelitis, and antibody responses against coagulation factor VIII in hemophilia A mice, even in animals previously sensitized to antigen. Only encapsulated rapamycin, not the free form, could induce immunological tolerance. Tolerogenic nanoparticle therapy represents a potential novel approach for the treatment of allergies, autoimmune diseases, and prevention of antidrug antibodies against biologic therapies.
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|a Juvenile Diabetes Research Foundation International
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|a en_US
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|a Article
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|t Proceedings of the National Academy of Sciences
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