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Polymeric synthetic nanoparticles for the induction of antigen-specific immunological tolerance.
Maldonado, Roberto A; LaMothe, Robert A; Ferrari, Joseph D; Zhang, Ai-Hong; Rossi, Robert J; Kolte, Pallavi N; Griset, Aaron P; O'Neil, Conlin; Altreuter, David H; Browning, Erica; Johnston, Lloyd; Farokhzad, Omid C; Langer, Robert; Scott, David W; von Andrian, Ulrich H; Kishimoto, Takashi Kei.
Afiliación
  • Maldonado RA; Selecta Biosciences, Inc., Watertown, MA 02472;
  • LaMothe RA; Selecta Biosciences, Inc., Watertown, MA 02472;
  • Ferrari JD; Selecta Biosciences, Inc., Watertown, MA 02472;
  • Zhang AH; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814;
  • Rossi RJ; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814;
  • Kolte PN; Selecta Biosciences, Inc., Watertown, MA 02472;
  • Griset AP; Selecta Biosciences, Inc., Watertown, MA 02472;
  • O'Neil C; Selecta Biosciences, Inc., Watertown, MA 02472;
  • Altreuter DH; Selecta Biosciences, Inc., Watertown, MA 02472;
  • Browning E; Selecta Biosciences, Inc., Watertown, MA 02472;
  • Johnston L; Selecta Biosciences, Inc., Watertown, MA 02472;
  • Farokhzad OC; Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115; King Abdulaziz University, Jeddah 22254, Saudi Arabia;
  • Langer R; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139; The David H. Koch Institute for Integrative Cancer Research, Cambridge, MA 02139;
  • Scott DW; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814;
  • von Andrian UH; Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115-6017; and The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard, Cambridge, MA 02139.
  • Kishimoto TK; Selecta Biosciences, Inc., Watertown, MA 02472; kkishimoto@selectabio.com.
Proc Natl Acad Sci U S A ; 112(2): E156-65, 2015 Jan 13.
Article en En | MEDLINE | ID: mdl-25548186
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Terapia de Inmunosupresión / Nanopartículas / Tolerancia Inmunológica / Antígenos Tipo de estudio: Prognostic_studies Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Terapia de Inmunosupresión / Nanopartículas / Tolerancia Inmunológica / Antígenos Tipo de estudio: Prognostic_studies Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos