|
 |
|
|||||||
|
|||||||||
Diabetes 54:1763-1769, 2005
© 2005 by the American Diabetes Association, Inc.
A Single Course of Anti-CD3 Monoclonal Antibody hOKT3
1(Ala-Ala) Results in Improvement in C-Peptide Responses and Clinical Parameters for at Least 2 Years after Onset of Type 1 Diabetes
1 Department of Medicine, Division of Endocrinology and the Naomi Berrie Diabetes Center, College of Physicians and Surgeons, Columbia University, New York, New York
2 Diabetes Center, University of California at San Francisco, San Francisco, California
3 Pacific Northwest Research Institute, Seattle, Washington
4 Department of Pediatrics, University of Utah, Salt Lake City, Utah
5 National Institutes of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland
Despite advances in understanding autoimmune diabetes in animal models, there has been little progress in altering the natural course of the human disease, which involves progression to insulin deficiency. Studies with immunosuppressive agents have shown short-term effectiveness, but they have not induced tolerance, and continuous treatment is needed. We studied the effects of hOKT3
1(Ala-Ala), a humanized Fc mutated anti-CD3 monoclonal antibody, on the progression of type 1 diabetes in patients with recent-onset disease in a randomized controlled trial. In general, the drug was well tolerated. A single course of treatment, within the first 6 weeks after diagnosis, preserved C-peptide responses to a mixed meal for 1 year after diagnosis (97 ± 9.6% of response at study entry in drug-treated patients vs. 53 ± 7.6% in control subjects, P < 0.01), with significant improvement in C-peptide responses to a mixed meal even 2 years after treatment (P < 0.02). The improved C-peptide responses were accompanied by reduced HbA1c and insulin requirements. Clinical responses to drug treatment were predicted by an increase in the relative number of CD8+ T-cells in the peripheral blood after the lymphocyte count recovered 2 weeks after the last dose of drug. We conclude that treatment with the anti-CD3 monoclonal antibody hOKT31(Ala-Ala) results in improved C-peptide responses and clinical parameters in type 1 diabetes for at least 2 years in the absence of continued immunosuppressive medications.
Address correspondence and reprint requests to Kevan Herold, MD, Associate Professor of Medicine, Columbia University, PH10-105, 630 W. 168th St., New York, NY 10032. E-mail: kh318{at}columbia.edu
Abbreviations: AUC, area under the response curve; mAb, monoclonal antibody; MMTT, mixed-meal tolerance test
CiteULike 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  B. Phillips, K. Nylander, J. Harnaha, J. Machen, R. Lakomy, A. Styche, K. Gillis, L. Brown, D. Lafreniere, M. Gallo, et al. A Microsphere-Based Vaccine Prevents and Reverses New-Onset Autoimmune Diabetes Diabetes, June 1, 2008; 57(6): 1544 - 1555. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Hadjiyanni and D. J. Drucker Glucagon-Like Peptide 1 and Type 1 Diabetes: NOD Ready for Prime Time? Endocrinology, November 1, 2007; 148(11): 5133 - 5135. [Full Text] [PDF]
|
|
|
|
 |
|
 B. Z. Alizadeh, G. Valdigem, M. J.H. Coenen, A. Zhernakova, B. Franke, A. Monsuur, P. L.C.M. van Riel, P. Barrera, T. R.D.J. Radstake, B. O. Roep, et al. Association analysis of functional variants of the FcgRIIa and FcgRIIIa genes with type 1 diabetes, celiac disease and rheumatoid arthritis Hum. Mol. Genet., November 1, 2007; 16(21): 2552 - 2559. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. A. Sherry, W. Chen, J. A. Kushner, M. Glandt, Q. Tang, S. Tsai, P. Santamaria, J. A. Bluestone, A.-M. B. Brillantes, and K. C. Herold Exendin-4 Improves Reversal of Diabetes in NOD Mice Treated with Anti-CD3 Monoclonal Antibody by Enhancing Recovery of {beta}-Cells Endocrinology, November 1, 2007; 148(11): 5136 - 5144. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. D. LYTTON, C. P. DENTON, and A. M. NUTZENBERGER Treatment of Autoimmune Disease with Rabbit Anti-T Lymphocyte Globulin: Clinical Efficacy and Potential Mechanisms of Action Ann. N.Y. Acad. Sci., September 1, 2007; 1110(1): 285 - 296. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. S. Eisenbarth Update in Type 1 Diabetes J. Clin. Endocrinol. Metab., July 1, 2007; 92(7): 2403 - 2407. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. You, B. Leforban, C. Garcia, J.-F. Bach, J. A. Bluestone, and L. Chatenoud Adaptive TGF-beta-dependent regulatory T cells control autoimmune diabetes and are a privileged target of anti-CD3 antibody treatment PNAS, April 10, 2007; 104(15): 6335 - 6340. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. ABLAMUNITS, N. A. SHERRY, J. A. KUSHNER, and K. C. HEROLD Autoimmunity and beta Cell Regeneration in Mouse and Human Type 1 Diabetes: The Peace Is Not Enough Ann. N.Y. Acad. Sci., April 1, 2007; 1103(1): 19 - 32. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Xu, J. Lee, E. Jankowska-Gan, J. Schultz, D. A. Roennburg, L. D. Haynes, S. Kusaka, H. W. Sollinger, S. J. Knechtle, A. M. VanBuskirk, et al. Human CD4+CD25low Adaptive T Regulatory Cells Suppress Delayed-Type Hypersensitivity during Transplant Tolerance J. Immunol., March 15, 2007; 178(6): 3983 - 3995. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Zhang, I. Todorov, C.-L. Lin, M. Atkinson, F. Kandeel, S. Forman, and D. Zeng Elimination of insulitis and augmentation of islet beta cell regeneration via induction of chimerism in overtly diabetic NOD mice PNAS, February 13, 2007; 104(7): 2337 - 2342. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Forestier, T. Takaki, A. Molano, J. S. Im, I. Baine, E. S. Jerud, P. Illarionov, R. Ndonye, A. R. Howell, P. Santamaria, et al. Improved Outcomes in NOD Mice Treated with a Novel Th2 Cytokine-Biasing NKT Cell Activator J. Immunol., February 1, 2007; 178(3): 1415 - 1425. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. A. Sherry, J. A. Kushner, M. Glandt, T. Kitamura, A.-M. B. Brillantes, and K. C. Herold Effects of Autoimmunity and Immune Therapy on {beta}-Cell Turnover in Type 1 Diabetes Diabetes, December 1, 2006; 55(12): 3238 - 3245. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L YOUNG, S. RAMANUJAN, H. T.C KREUWEL, C. C. WHITING, K. G GADKAR, and L. K.M SHODA Mechanisms Mediating Anti-CD3 Antibody Efficacy: Insights from a Mathematical Model of Type 1 Diabetes Ann. N.Y. Acad. Sci., October 1, 2006; 1079(1): 369 - 373. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. M. Gillespie Type 1 diabetes: pathogenesis and prevention. Can. Med. Assoc. J., July 18, 2006; 175(2): 165 - 170. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Endocrinology & Metabolism News, July 2005 J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 17a - 17a. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Diabetes | Diabetes Care | Clinical Diabetes | Diabetes Spectrum |