(Journal Article): Treatment of type 1 diabetes mellitus with DAB486-IL2, a toxin conjugate witch targets activated T-lymphocytes
 
Boitard C, Timsit J, Assan R, Mogenet A, Debussche X, Kaloustlan E, Attali JR, Chanson P, Chatenoud L, Woodworth T, et al. (Institut National de la Santé et de la Recherche Médicale U561, St. Vincent de Paul Hospital, Paris, France., christian.boitard@paris5.inserm.fr )
 
IN: Diabetologia 1992; 35(suppl 1):A218
Impact Factor(s) of Diabetologia: 5.583 (2004), 5.689 (2003), 5.136 (2002), 6.299 (2001)

ABSTRACT: Evidence point to autoreactive T-Iymphocytes in the pathogenesis of insulin-¬dependent diabetes mellitus (IDDM). Treatment with Cyclosporin A (7.5-10 mg/kg/d) of IDDM patients induced remission and partial recovery of insulin secretion, but nephrotoxicity and relapses occurred. Therapeutics with no major side effect and a more selective action on T-Iymphocytes committed to beta-cell destruction are thus required. In a phase I/II trial 18 IDDM patients were treated with DAB486-IL-2 (0.025, 0.05 and 0.075 mg/kg/d, for 7 days, 6 patients in each group) which selectively targets activated T-Iymphocytes expressing high affinity lL-2 receptors, then with Cyclosporin A (5 mg/kg/d) 5 weeks later. Insulin needs decreased from 0.79 ± 0.24 to 0.30 ± 0.15 UI/kg/d within 6 weeks. Among 8 patients followed for 8 months 4 required less than 0.1 UI/kg/d (HbA1c 5.9 ± 0.6%) within 3 months of Cyclosporin A. Fasting C peptide levels increased from 0.20 ± 0.12 nM/L at start to 0.36 ± 0.20 (n=18) at week 6, and to 0.48 ± 0.31 (n=9) after 3 months of Cyclosporin A. Corresponding glucagon-stimulated C peptide values increased from 0.37 ± 0.22 to 0.62 ± 0.34, and to 0.93 ± 0.63, respectively. Treatment with DAB486-IL-2 had minimal and transient side effects (transaminases > 2N in 7, mild fever in 7). Plasma creatinine increased by less than 8% at 8 months. This pilot study opens new directions in immunotherapy and prompts to a randomized trial.

TYPE OF PUBLICATION: Original article

Articles citing this article:

• Saudek F, Havrdova T, Boucek P, Karasova L, Novota P, Skibova J. Polyclonal Anti-T-Cell Therapy for Type 1 Diabetes Mellitus of Recent Onset. Rev Diabetic Stud 2004. 2: 80-88.
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