Immunomodulation in type 1 diabetes by NBI-6024, an altered peptide ligand of the insulin B(9-23) epitope

D. G. Alleva, R. A. Maki, A. L. Putnam, J. M. Robinson, M. S. Kipnes, P. Dandona, J. B. Marks, D. L. Simmons, C. J. Greenbaum, R. G. Jimenez, P. J. Conlon, P. A. Gottlieb

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60 Scopus citations

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-γ-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.

Original languageEnglish (US)
Pages (from-to)59-69
Number of pages11
JournalScandinavian Journal of Immunology
Volume63
Issue number1
DOIs
StatePublished - Jan 1 2006

ASJC Scopus subject areas

  • Immunology

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    Alleva, D. G., Maki, R. A., Putnam, A. L., Robinson, J. M., Kipnes, M. S., Dandona, P., Marks, J. B., Simmons, D. L., Greenbaum, C. J., Jimenez, R. G., Conlon, P. J., & Gottlieb, P. A. (2006). Immunomodulation in type 1 diabetes by NBI-6024, an altered peptide ligand of the insulin B(9-23) epitope. Scandinavian Journal of Immunology, 63(1), 59-69. https://doi.org/10.1111/j.1365-3083.2005.01705.x