Uveitis Therapy With Shark Variable Novel Antigen Receptor Domains Targeting Tumor Necrosis Factor Alpha or Inducible T-Cell Costimulatory Ligand.

ABSTRACT:

Purpose

We assess the efficacy of two next-generation biologic therapies in treating experimental autoimmune uveitis.

Methods

Variable binding domains from shark immunoglobulin novel antigen receptors (VNARs) were fused with a mouse IgG2a constant domain (Fc) to generate VNAR-Fc molecules with binding specificity to tumor necrosis factor alpha (TNFα) or inducible T-cell costimulatory ligand (ICOSL). Treatment with VNAR-Fc fusion proteins was compared to treatment with dexamethasone or vehicle in the Lewis rat model of experimental autoimmune uveitis (EAU). Inflammation control was determined by comparing OCT clinical and histologic scores, and aqueous humor protein concentration. The concentration of 27 inflammatory cytokines in the aqueous humor was measured using a multipl

SUBMITTER: Pepple KL 

PROVIDER: S-EPMC6753974 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature