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dc.contributor.authorPickens, Chad J.
dc.contributor.authorChristopher, Matthew A.
dc.contributor.authorLeon, Martin A.
dc.contributor.authorPressnall, Melissa M.
dc.contributor.authorJohnson, Stephanie N.
dc.contributor.authorThati, Sharadvi
dc.contributor.authorSullivan, Bradley P.
dc.contributor.authorBerkland, Cory
dc.date.accessioned2020-12-15T20:38:54Z
dc.date.available2020-12-15T20:38:54Z
dc.date.issued2019-05-14
dc.identifier.citationPickens, 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.9b00063en_US
dc.identifier.urihttp://hdl.handle.net/1808/30978
dc.descriptionThis 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.abstractMultiple 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.sponsorshipNational Institutes of Health Graduate Training Program in Dynamic Aspects of Chemical Biology Grant (T32 GM008545)en_US
dc.description.sponsorshipHoward Rytting pre-doctoral fellowship from the Department of Pharmaceutical Chemistry at the University of Kansasen_US
dc.description.sponsorshipNational Institutes of Health Biotechnology Training Grant (NIH0073415)en_US
dc.description.sponsorshipNIH Shared Instrumentation Grant # S10RR024664en_US
dc.description.sponsorshipNSF Major Research Instrumentation Award # 1625923en_US
dc.publisherAmerican Chemical Societyen_US
dc.rightsCopyright © 2019 American Chemical Societyen_US
dc.subjectAutoimmunityen_US
dc.subjectAntigen-specific immunotherapyen_US
dc.subjectCopper-catalyzed azide-alkyne cycloadditionen_US
dc.subjectExperimental autoimmune encephalomyelitisen_US
dc.subjectAntigen-drug conjugateen_US
dc.titleAntigen-Drug Conjugates as a Novel Therapeutic Class for the Treatment of Antigen-Specific Autoimmune Disordersen_US
dc.typeArticleen_US
kusw.kuauthorPickens, Chad J.
kusw.kuauthorChristopher, Matthew A.
kusw.kuauthorLeon, Martin A.
kusw.kuauthorPressnall, Melissa M.
kusw.kuauthorJohnson, Stephanie N.
kusw.kuauthorThati, Sharadvi
kusw.kuauthorSullivan, Bradley P.
kusw.kuauthorBerkland, Cory
kusw.kudepartmentPharmaceutical Chemistryen_US
kusw.kudepartmentChemistryen_US
dc.identifier.doi10.1021/acs.molpharmaceut.9b00063en_US
dc.identifier.orcidhttps://orcid.org/0000-0002-5008-8771en_US
dc.identifier.orcidhttps://orcid.org/0000-0002-9346-938Xen_US
kusw.oaversionScholarly/refereed, author accepted manuscripten_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US
dc.identifier.pmidPMC7590940en_US
dc.rights.accessrightsopenAccessen_US


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