Anti-CD3 Therapy

(Journal Article): Questioning Four Preconceived Ideas on Immunotherapy of Clinical Type 1 Diabetes: Lessons from Recent CD3 Antibody Trials
 
Chatenoud L, Bach JF (Université René Descartes Paris 5, INSERM U580, Hôpital Necker-Enfants Malades, Paris, France., bach(at)necker.fr )
 
IN: Rev Diabetic Stud 2005; 2(3):116-120
Impact Factor(s) of Rev Diabetic Stud: 0.125 (2006)

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ABSTRACT: n.a.

TYPE OF PUBLICATION: Review

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36. Herold KC, Hagopian W, Auger JA, Poumian Ruiz E, Taylor L, Donaldson D, Gitelman SE, Harlan DM, Xu D, Zivin RA, et al. Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus. N Engl J Med 2002. 346:1692-1698.
37. Herold KC, Gitelman SE, Masharani U, Hagopian W, Bisikirska B, Donaldson D, Rother K, Diamond B, Harlan DM, Bluestone JA. A single course of anti-CD3 monoclonal antibody hOKT3gamma1(Ala-Ala) results in improvement in C-peptide responses and clinical parameters for at least 2 years after onset of type 1 diabetes. Diabetes 2005. 54:1763-1769.
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Articles citing this article:

• Sia C, Weinem M. "Persistence of Diabetes" - Why Has Research into Type 1 Diabetes not Made Significant Advances? Rev Diabet Stud 2006. 3: 156-160.
  » Diabetes OD » Reversal/Prevention of Diabete... » T1DM » Journal Article 

(Journal Article): Insulin-dependent diabetes mellitus as an autoimmune disease.
 
Bach JF (INSERM U 25, Hopital Necker, Paris, France.)
 
IN: Endocr Rev 1994; 15(4):516-542
Impact Factor(s) of Endocr Rev: 18.784 (2004), 17.324 (2003), 21.643 (2002), 26.456 (2001)

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ABSTRACT: IDDM is unquestionably an autoimmune disease, as reflected by the presence of beta-cell-reactive autoantibodies and T cells, T cell-mediated transfer of the disease in nondiabetic mice, rats, and humans, and disease sensitivity to immunosuppressive therapy. T cells are predominantly, if not exclusively, involved in creating the islet lesions that lead to beta-cell atrophy after a stage of reversible inflammation. A full understanding of the disease pathogenesis will require a better definition of the nature of the triggering and target autoantigen(s) and of the effector mechanisms (cytokines, cytotoxic cells?). Much less information is available on the etiology than on the pathogenesis. Genetic factors are mandatory and the involvement of predisposition genes (HLA and non-HLA) is now being unravelled. The modulatory role of environmental factors is demonstrated by the high disease discordance rate in identical twins and by experimental data showing positive and negative modulation of the disease by a number of agents, notably infectious agents and food constituents. It is not clear, however, whether a given environmental factor, e.g. a precise virus or a cow's milk component, plays a real etiological role in a selected genetic background. IDDM thus appears as a multifactorial disease. It is not known, however, whether all factors intervene concomitantly in a given individual or separately in subsets of patients, explaining the clinical heterogeneity of the disease. The mechanisms underlying the loss of tolerance to self beta-cell autoantigen(s) are still unknown. Defective intrathymic negative selection of autoantigen-specific autoreactive T cell clones is unlikely. Breakdown of T cell anergy could occur according to various mechanisms, including aberrant expression of MHC molecules and molecular mimicry. Defective suppressor T cell function, perhaps related to TH1/TH2 imbalance, probably intervenes by amplifying the anti-beta-cell autoimmune response whatever its triggering mechanism. Before putative etiological agents are identified, one must base immunotherapy on nonantigen-specific agents. Results recently obtained in NOD mice indicate that the goal of nontoxic long-lasting immune protection from the disease is feasible if treatment is started early enough. In some cases (anti-T cell monoclonal antibodies), it appears that specific unresponsiveness can be induced. This double strategy (early intervention, tolerance induction) is the main challenge for immunodiabetologists.

TYPE OF PUBLICATION: Review

Articles citing this article:

• Throsby M, Coulaud J, Durant S, Homo-Delarche F. Increased Transcriptional Preproinsulin II Beta-Cell Activity in Neonatal Nonobese Diabetic Mice: In Situ Hybridization Analysis. Rev Diabetic Stud 2005. 2: 75-83.
  » Diabetes OD » Diabetes Pathogenesis » T1DM » Autoimmunity » NOD mouse » Hyperinsulinemia » Journal Article 

(Journal Article): Limitations in Immunotherapy with CD3 Antibodies: Comment on the Article by Drs. Chatenoud and Bach
 
Bresson D, von Herrath M (La Jolla Institute for Allergy and Immunology, Department of Developmental Immunology 3, 10355 Science Center Drive, San Diego, California 92121, USA, matthias(at)liai.org )
 
IN: Rev Diabetic Stud 2005; 20(4):187-189
Impact Factor(s) of Rev Diabetic Stud: 0.125 (2006)

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ABSTRACT: n.a.

TYPE OF PUBLICATION: Comment

REFERENCES:

1. Chatenoud L, Bach JF. Questioning four preconceived ideas on immunotherapy of clinical type 1 diabetes: lessons from recent CD3 antibody trials. Rev Diabetic Stud 2005. 2(3):116-120.
2. Herold KC, Hagopian W, Auger JA, Poumian-Ruiz E, Taylor L, Donaldson D, Gitelman SE, Harlan DM, Xu D, Zivin RA, Bluestone JA. Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus. N Engl J Med 2002. 346(22):1692-1698.
3. Keymeulen B, Vandemeulebroucke E, Ziegler AG, Mathieu C, Kaufman L, Hale G, Gorus F, Goldman M, Walter M, Candon S, et al. Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes. N Engl J Med 2005. 352(25):2598-608.
4. Herold KC, Gitelman SE, Masharani U, Hagopian W, Bisikirska B, Donaldson D, Rother K, Diamond B, Harlan DM, Bluestone JA. A single course of anti-CD3 monoclonal antibody hOKT3gamma1(Ala-Ala) results in improvement in C-peptide responses and clinical parameters for at least 2 years after onset of type 1 diabetes. Diabetes 2005. 54(6):1763-1769.
5. Hirsch R, Gress RE, Pluznik DH, Eckhaus M, Bluestone JA. Effects of in vivo administration of anti-CD3 monoclonal antibody on T cell function in mice. II. In vivo activation of T cells. J Immunol 1989. 142(3):737-743.
6. Ferran C, Sheehan K, Dy M, Schreiber R, Merite S, Landais P, Noel LH, Grau G, Bluestone J, Bach JF. Cytokine-related syndrome following injection of anti-CD3 monoclonal antibody: further evidence for transient in vivo T cell activation. Eur J Immunol 1990. 20(3):509-515.
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9. Herold KC, Bluestone JA, Montag AG, Parihar A, Wiegner A, Gress RE, Hirsch R. Prevention of autoimmune diabetes with nonactivating anti-CD3 monoclonal antibody. Diabetes 1992. 41(3):385-391.
10. von Herrath MG, Coon B, Wolfe T, Chatenoud L. Nonmitogenic CD3 antibody reverses virally induced (rat insulin promoter-lymphocytic choriomeningitis virus) autoimmune diabetes without impeding viral clearance. J Immunol 2002. 168(2):933-941.
11. Wu AJ, Hua H, Munson SH, McDevitt HO. Tumor necrosis factor-alpha regulation of CD4+CD25+ T cell levels in NOD mice. Proc Natl Acad Sci U S A 2002. 99(19):12287-12292.
12. Kukreja A, Cost G, Marker J, Zhang C, Sun Z, Lin-Su K, Ten S, Sanz M, Exley M, Wilson B, et al. Multiple immuno-regulatory defects in type-1 diabetes. J Clin Invest. 2002. 109(1):131-140.
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16. Diabetes Prevention Trial - Type 1 Diabetes Study Group. Effects of insulin in relatives of patients with type 1 diabetes mellitus. N Engl J Med 2002. 346(22):1685-1691.

Articles citing this article:

• Sia C, Weinem M. "Persistence of Diabetes" - Why Has Research into Type 1 Diabetes not Made Significant Advances? Rev Diabet Stud 2006. 3: 156-160.
  » Diabetes OD » Reversal/Prevention of Diabete... » T1DM » Journal Article 

(Journal Article): Response to the Comment by D. Bresson and M. von Herrath
 
Chatenoud L, Bach JF (Université René Descartes Paris 5, INSERM U580, Hôpital Necker-Enfants Malades, Paris, France, bach(at)necker.fr )
 
IN: Rev Diabetic Stud 2005; 2(4):190-191
Impact Factor(s) of Rev Diabetic Stud: 0.125 (2006)

Fulltext:    HTML  PDF

ABSTRACT: n.a.

TYPE OF PUBLICATION: Comment

REFERENCES:

1. Herold KC, Bluestone JA, Montag AG, Parihar A, Wiegner A, Gress RE, Hirsch R. Prevention of autoimmune diabetes with nonactivating anti-CD3 monoclonal antibody. Diabetes 1992. 41:385-391.
2. Chatenoud L, Thervet E, Primo J, Bach JF. Rémission de la maladie établie chez la souris NOD diabétique par l'anticorps monoclonal anti-CD3. C. R. Acad. Sci. III 1992. 315:225-228.
3. Chatenoud L, Thervet E, Primo J, Bach JF. Anti-CD3 antibody induces long-term remission of overt autoimmunity in nonobese diabetic mice. Proc. Natl. Acad. Sci. USA 1994. 91:123-127.
4. Von Herrath MG, Coon B, Wolfe T, Chatenoud L. Nonmitogenic CD3 antibody reverses virally induced (rat insulin promoter-lymphocytic choriomeningitis virus) autoimmune diabetes without impeding viral clearance. J. Immunol. 2002. 168:933-941.