Polymeric synthetic nanoparticles for the induction of antigen-specific immunological tolerance
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, biodegrad...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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National Academy of Sciences (U.S.)
2015
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| Online Access: | http://hdl.handle.net/1721.1/97585 https://orcid.org/0000-0003-4255-0492 |
| _version_ | 1826189067028529152 |
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| author | Maldonado, Roberto A. LaMothe, Robert A. Ferrari, Joseph D. Zhang, Ai-Hong Rossi, Robert J. Kolte, Pallavi N. Griset, Aaron P. O'Neil, Conlin P. Altreuter, David H. Browning, Erica A. Johnston, Lloyd P. M. Farokhzad, Omid C. Scott, David W. von Andrian, Ulrich H. Kishimoto, Takashi Kei Langer, Robert S |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Maldonado, Roberto A. LaMothe, Robert A. Ferrari, Joseph D. Zhang, Ai-Hong Rossi, Robert J. Kolte, Pallavi N. Griset, Aaron P. O'Neil, Conlin P. Altreuter, David H. Browning, Erica A. Johnston, Lloyd P. M. Farokhzad, Omid C. Scott, David W. von Andrian, Ulrich H. Kishimoto, Takashi Kei Langer, Robert S |
| author_sort | Maldonado, Roberto A. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T08:09:01Z |
| format | Article |
| id | mit-1721.1/97585 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:09:01Z |
| publishDate | 2015 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/975852022-09-23T11:12:58Z 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 P. Altreuter, David H. Browning, Erica A. Johnston, Lloyd P. M. Farokhzad, Omid C. Scott, David W. von Andrian, Ulrich H. Kishimoto, Takashi Kei Langer, Robert S Massachusetts Institute of Technology. Department of Chemical Engineering Koch Institute for Integrative Cancer Research at MIT Langer, Robert 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. Juvenile Diabetes Research Foundation International 2015-06-30T16:37:56Z 2015-06-30T16:37:56Z 2014-12 2014-05 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/97585 Maldonado, Roberto A., Robert A. LaMothe, Joseph D. Ferrari, Ai-Hong Zhang, Robert J. Rossi, Pallavi N. Kolte, Aaron P. Griset, et al. “Polymeric Synthetic Nanoparticles for the Induction of Antigen-Specific Immunological Tolerance.” Proceedings of the National Academy of Sciences 112, no. 2 (December 29, 2014): E156–E165. https://orcid.org/0000-0003-4255-0492 en_US http://dx.doi.org/10.1073/pnas.1408686111 Proceedings of the National Academy of Sciences Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences (U.S.) National Academy of Sciences (U.S.) |
| spellingShingle | Maldonado, Roberto A. LaMothe, Robert A. Ferrari, Joseph D. Zhang, Ai-Hong Rossi, Robert J. Kolte, Pallavi N. Griset, Aaron P. O'Neil, Conlin P. Altreuter, David H. Browning, Erica A. Johnston, Lloyd P. M. Farokhzad, Omid C. Scott, David W. von Andrian, Ulrich H. Kishimoto, Takashi Kei Langer, Robert S Polymeric synthetic nanoparticles for the induction of antigen-specific immunological tolerance |
| title | Polymeric synthetic nanoparticles for the induction of antigen-specific immunological tolerance |
| title_full | Polymeric synthetic nanoparticles for the induction of antigen-specific immunological tolerance |
| title_fullStr | Polymeric synthetic nanoparticles for the induction of antigen-specific immunological tolerance |
| title_full_unstemmed | Polymeric synthetic nanoparticles for the induction of antigen-specific immunological tolerance |
| title_short | Polymeric synthetic nanoparticles for the induction of antigen-specific immunological tolerance |
| title_sort | polymeric synthetic nanoparticles for the induction of antigen specific immunological tolerance |
| url | http://hdl.handle.net/1721.1/97585 https://orcid.org/0000-0003-4255-0492 |
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