Immunomodulation in Type 1 Diabetes by NBI‐6024, an Altered Peptide Ligand of the Insulin B(9−23) Epitope

Neurocrine Biosciences, Inc., San Diego, CA 92130, USA.
Scandinavian Journal of Immunology (Impact Factor: 1.88). 02/2006; 63(1):59-69. DOI: 10.1111/j.1365-3083.2005.01705.x
Source: PubMed

ABSTRACT NBI-6024 is an altered peptide ligand (APL) corresponding to the 9-23 amino acid region of the insulin B chain (B(9-23)), an epitope recognized by inflammatory interferon-gamma-producing T helper (Th)1 lymphocytes in type 1 diabetic patients. Immunomodulatory effects of NBI-6024 administration in recent-onset diabetic patients in a phase I clinical trial (NBI-6024-0003) were measured in peripheral blood mononuclear cells using the enzyme-linked immunosorbent spot assay. Analysis of the mean magnitude of cytokine responses to B(9-23) and NBI-6024 for each cohort showed significant increases in interleukin-5 responses (a Th2 regulatory phenotype) in cohorts that received APL relative to those receiving placebo. A responder analysis showed that Th1 responses to B(9-23) and NBI-6024 were observed almost exclusively in the placebo-treated diabetic population but not in nondiabetic control subjects and that APL administration (five biweekly subcutaneous injections) significantly and dose-dependently reduced the percentage of patients with these Th1 responses. The results of this phase I clinical study strongly suggest that NBI-6024 treatment shifted the Th1 pathogenic responses in recent-onset type 1 diabetic patients to a protective Th2 regulatory phenotype. The significance of these findings on the clinical outcome of disease is currently under investigation in a phase II multidose study.

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Available from: Rich A Maki, Oct 16, 2014
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