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Soluble Antigen Arrays Efficiently Deliver Peptides and Arrest Spontaneous Autoimmune Diabetes.
Firdessa-Fite, Rebuma; Johnson, Stephanie N; Leon, Martin A; Khosravi-Maharlooei, Mohsen; Baker, Rocky L; Sestak, Joshua O; Berkland, Cory; Creusot, Remi J.
Afiliación
  • Firdessa-Fite R; Columbia Center for Translational Immunology, Department of Medicine and Naomi Berrie Diabetes Center, Columbia University Medical Center, New York, NY.
  • Johnson SN; Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS.
  • Leon MA; Department of Chemistry, University of Kansas, Lawrence, KS.
  • Khosravi-Maharlooei M; Columbia Center for Translational Immunology, Department of Medicine and Naomi Berrie Diabetes Center, Columbia University Medical Center, New York, NY.
  • Baker RL; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO.
  • Sestak JO; Orion BioScience, Inc., Omaha, NE.
  • Berkland C; Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS.
  • Creusot RJ; Bioengineering Graduate Program, University of Kansas, Lawrence, KS.
Diabetes ; 70(6): 1334-1346, 2021 06.
Article en En | MEDLINE | ID: mdl-33468513
Antigen-specific immunotherapy (ASIT) offers a targeted treatment of autoimmune diseases that selectively inhibits autoreactive lymphocytes, but there remains an unmet need for approaches that address the limited clinical efficacy of ASIT. Soluble antigen arrays (SAgAs) deliver antigenic peptides or proteins in multivalent form, attached to a hyaluronic acid backbone using either hydrolysable linkers (hSAgAs) or stable click chemistry linkers (cSAgAs). They were evaluated for the ability to block spontaneous development of disease in a nonobese diabetic mouse model of type 1 diabetes (T1D). Two peptides, a hybrid insulin peptide and a mimotope, efficiently prevented the onset of T1D when delivered in combination as SAgAs, but not individually. Relative to free peptides administered at equimolar dose, SAgAs (particularly cSAgAs) enabled a more effective engagement of antigen-specific T cells with greater persistence and induction of tolerance markers, such as CD73, interleukin-10, programmed death-1, and KLRG-1. Anaphylaxis caused by free peptides was attenuated using hSAgA and obviated using cSAgA platforms. Despite similarities, the two peptides elicited largely nonoverlapping and possibly complementary responses among endogenous T cells in treated mice. Thus, SAgAs offer a novel and promising ASIT platform superior to free peptides in inducing tolerance while mitigating risks of anaphylaxis for the treatment of T1D.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos / Análisis por Matrices de Proteínas / Diabetes Mellitus Tipo 1 Límite: Animals Idioma: En Revista: Diabetes Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos / Análisis por Matrices de Proteínas / Diabetes Mellitus Tipo 1 Límite: Animals Idioma: En Revista: Diabetes Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos