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Anti-Cytokine Active Immunotherapy Based on Supramolecular Peptides for Alleviating IL-1ß-Mediated Inflammation.
Shetty, Shamitha; Wu, Yaoying; Lloyd, Christopher Z; Mehta, Nalini; Liu, Yining; Woodruff, Mia E; Segura, Tatiana; Collier, Joel H.
Afiliación
  • Shetty S; Department of Biomedical Engineering, Duke University, Durham, NC, 27705, USA.
  • Wu Y; Department of Biomedical Engineering, Duke University, Durham, NC, 27705, USA.
  • Lloyd CZ; Department of Biomedical Engineering, Duke University, Durham, NC, 27705, USA.
  • Mehta N; Department of Biomedical Engineering, Duke University, Durham, NC, 27705, USA.
  • Liu Y; Department of Biomedical Engineering, Duke University, Durham, NC, 27705, USA.
  • Woodruff ME; Department of Biomedical Engineering, Duke University, Durham, NC, 27705, USA.
  • Segura T; Department of Biomedical Engineering, Duke University, Durham, NC, 27705, USA.
  • Collier JH; Department of Biomedical Engineering, Duke University, Durham, NC, 27705, USA.
Adv Healthc Mater ; : e2401444, 2024 Aug 07.
Article en En | MEDLINE | ID: mdl-39113323
ABSTRACT
IL-1ß is a principal proinflammatory cytokine underlying multiple local and systemic chronic inflammatory conditions including psoriasis, rheumatoid arthritis, inflammatory bowel disease, and type 2 diabetes. Passive immunotherapies and biologic drugs targeting IL-1ß, while offering significant clinical benefit, nevertheless have limitations such as significant non-response rates, induction of anti-drug antibodies, and high costs. Here, an active immunotherapy raising antibody responses against IL-1ß employing self-assembling peptide nanofibers is described. The nanofibers contain defined quantities of B-cell epitopes from IL-1ß and exogenous T helper epitopes and employ the Q11 self-assembling peptide platform. Without adjuvant, the nanofibers raised durable anti-IL-1ß antibody responses that inhibit IL-1ß activity in vitro and in vivo. In a mouse model of imiquimod-induced psoriasis, prophylactic immunizations with the nanofibers diminished symptoms of epidermal thickening. This therapeutic effect is associated with biasing the immune response toward an anti-inflammatory IgG1/Th2 phenotype and a lowered expression of proinflammatory genes in the skin. Further, anti-IL-1ß nanofibers induced therapeutic immunosuppressive CD62L+ Treg cells. This technology represents a potential alternative for passive immunotherapies and other biologics for treating chronic inflammatory conditions.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Adv Healthc Mater Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Adv Healthc Mater Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania