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Antigen-Drug Conjugates as a Novel Therapeutic Class for the Treatment of Antigen-Specific Autoimmune Disorders
dc.contributor.author | Pickens, Chad J. | |
dc.contributor.author | Christopher, Matthew A. | |
dc.contributor.author | Leon, Martin A. | |
dc.contributor.author | Pressnall, Melissa M. | |
dc.contributor.author | Johnson, Stephanie N. | |
dc.contributor.author | Thati, Sharadvi | |
dc.contributor.author | Sullivan, Bradley P. | |
dc.contributor.author | Berkland, Cory | |
dc.date.accessioned | 2020-12-15T20:38:54Z | |
dc.date.available | 2020-12-15T20:38:54Z | |
dc.date.issued | 2019-05-14 | |
dc.identifier.citation | Pickens, C. J., Christopher, M. A., Leon, M. A., Pressnall, M. M., Johnson, S. N., Thati, S., Sullivan, B. P., & Berkland, C. (2019). Antigen-Drug Conjugates as a Novel Therapeutic Class for the Treatment of Antigen-Specific Autoimmune Disorders. Molecular pharmaceutics, 16(6), 2452–2461. https://doi.org/10.1021/acs.molpharmaceut.9b00063 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/30978 | |
dc.description | This document is the Accepted Manuscript version of a Published Work that appeared in final form in Molecular Pharmaceutics, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see doi.org/10.1021/acs.molpharmaceut.9b00063. | en_US |
dc.description.abstract | Multiple sclerosis represents the world’s most common cause of neurological disability in young people and is attributed to a loss of immune tolerance toward proteins of the myelin sheath. Typical treatment options for MS patients involve immunomodulatory drugs, which act non-specifically, resulting in global immunosuppression. The study discussed herein aims to demonstrate the efficacy of antigen-specific immunotherapies involving conjugation of disease causing auto-antigen, PLP139–151, and a potent immunosuppressant, dexamethasone. Antigen-drug conjugates (AgDCs) were formed using copper-catalyzed azide-alkyne cycloaddition chemistry with the inclusion of a hydrolyzable linker to maintain activity of released dexamethasone. Subcutaneous administration of this antigen-drug conjugate to SJL mice induced with experimental autoimmune encephalomyelitis protected the mice from symptom onset throughout the 25-day study, demonstrating enhanced efficacy in comparison to dexamethasone treatment. These results highlight the benefits of co-delivery of auto-antigens with immunosuppressant drugs as AgDCs for the treatment of autoimmune diseases. | en_US |
dc.description.sponsorship | National Institutes of Health Graduate Training Program in Dynamic Aspects of Chemical Biology Grant (T32 GM008545) | en_US |
dc.description.sponsorship | Howard Rytting pre-doctoral fellowship from the Department of Pharmaceutical Chemistry at the University of Kansas | en_US |
dc.description.sponsorship | National Institutes of Health Biotechnology Training Grant (NIH0073415) | en_US |
dc.description.sponsorship | NIH Shared Instrumentation Grant # S10RR024664 | en_US |
dc.description.sponsorship | NSF Major Research Instrumentation Award # 1625923 | en_US |
dc.publisher | American Chemical Society | en_US |
dc.rights | Copyright © 2019 American Chemical Society | en_US |
dc.subject | Autoimmunity | en_US |
dc.subject | Antigen-specific immunotherapy | en_US |
dc.subject | Copper-catalyzed azide-alkyne cycloaddition | en_US |
dc.subject | Experimental autoimmune encephalomyelitis | en_US |
dc.subject | Antigen-drug conjugate | en_US |
dc.title | Antigen-Drug Conjugates as a Novel Therapeutic Class for the Treatment of Antigen-Specific Autoimmune Disorders | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Pickens, Chad J. | |
kusw.kuauthor | Christopher, Matthew A. | |
kusw.kuauthor | Leon, Martin A. | |
kusw.kuauthor | Pressnall, Melissa M. | |
kusw.kuauthor | Johnson, Stephanie N. | |
kusw.kuauthor | Thati, Sharadvi | |
kusw.kuauthor | Sullivan, Bradley P. | |
kusw.kuauthor | Berkland, Cory | |
kusw.kudepartment | Pharmaceutical Chemistry | en_US |
kusw.kudepartment | Chemistry | en_US |
dc.identifier.doi | 10.1021/acs.molpharmaceut.9b00063 | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-5008-8771 | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-9346-938X | en_US |
kusw.oaversion | Scholarly/refereed, author accepted manuscript | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC7590940 | en_US |
dc.rights.accessrights | openAccess | en_US |