A Non-Activating “Humanized” Anti-Cd3 Monoclonal Antibody Retains Immunosuppressive Properties in Vivo

Alegre, Maria Luisa; Peterson, Laura; Xu, Danlin; Sattar, Husain; Jeyarajah, D. Rohan; Kowalkowski, Kenneth; Thistlethwaite, J. Richard; Zivin, Robert A.; Jolliffe, Linda K.; Bluestone, Jeffrey A.

doi:10.1097/00007890-199457110-00001

Cited by 158 publications

(22 citation statements)

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“…This explains that, in vitro and in vivo, the mitogenic response varies with the antibody isotype (murine IgG 2 a ) IgG 1 ) IgG 2 b ) IgA) and that CD3-specific F(ab 0 )2 fragments, lacking the Fc portion, are non-mitogenic [17,18,[28][29][30]. The fact that non-mitogenic F(ab 0 )2 fragments fully retain their therapeutic activity was the rationale behind the engineering of non-Fc receptor binding humanised CD3-specific antibodies [17,[31][32][33][34][35]. It is important to emphasize that nonFc binding CD3-specific antibodies still trigger partial signalling both in vitro and in vivo, an effect that appears to be essential for their therapeutic activity [17,36,37].…”

Section: Mitogenicity/lymphocyte Signallingmentioning

confidence: 99%

“…The advent of humanised CD3-specific antibodies was an essential milestone in their clinical development, as it enabled the manufacture of non-Fc-binding antibodies, which are devoid of the deleterious massive cytokinereleasing activity [34,35].…”

Section: Humanised Non-mitogenic Cd3 Antibodiesmentioning

confidence: 99%

“…Firstly, OKT3g1 Ala-Ala, the humanised version of OKT3, exhibits two mutations in its Fc portion [35]. Secondly, ChAglyCD3, derived from the rat YTH 12.5 antibody, expresses a single mutation that prevents glycosylation of its g1 Fc portion [34].…”

Section: Humanised Non-mitogenic Cd3 Antibodiesmentioning

confidence: 99%

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CD3-specific antibodies restore self-tolerance: mechanisms and clinical applications

Chatenoud

2005

Current Opinion in Immunology

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Section: Mitogenicity/lymphocyte Signallingmentioning

confidence: 99%

Section: Humanised Non-mitogenic Cd3 Antibodiesmentioning

confidence: 99%

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CD3-specific antibodies restore self-tolerance: mechanisms and clinical applications

Chatenoud

2005

Current Opinion in Immunology

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“…The Fc region of these anti-nmCD3 antibodies has been engineered to enhance efficacy and safety [3,14,125]. Herold and colleagues treated patients within six weeks of diagnosis with a single course of anti-nmCD3 antibody and monitored β-cell function by measuring C-peptide responses over two years [57,58].…”

Section: Targeting T Cells With Antibodiesmentioning

confidence: 99%

Immunotherapy of type 1 diabetes

Tisch

et al. 2008

Arch. Immunol. Ther. Exp.

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Type 1 diabetes (T1D) is an autoimmune disease in which the insulin-producing beta cells are destroyed. Diabetic patients manage their hyperglycemia by daily insulin injections. However, insulin therapy is by no means a cure. Accordingly, a significant effort has been ongoing to develop immunotherapies that effectively prevent and/or treat T1D in the clinic. This review focuses on antigen- and antibody-based immunotherapies and discusses the respective strengths and weaknesses of these approaches.

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“…Similar results were obtained in humans. The mechanism appears to be related to the induction of CD4+ CD25+ regulatory T cells [44,45].…”

Section: Duration Of Treatmentmentioning

confidence: 99%

Treatment of autoimmune hepatitis: Current and future therapies

Álvarez

2004

Curr Treat Options Gastro

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Autoimmune hepatitis is an uncommon liver disease affecting children and adults. Early diagnosis and start of treatment improve the response and long-term outcome. Initial treatment depends on patient's age and the clinical, laboratory, and histological features that allow the prediction of the response, as well as the presence or absence of associated extrahepatic disorders. In specialized centers, short-term cyclosporine is used safely and successfully to control the liver inflammatory process. Low doses of prednisone in association with azathioprine are sufficient to sustain the response. Maintenance treatment must be administered for several years, and withdrawal can be attempted after at least 4 years of a complete and sustained response. Future research should focus on the recovery of immune homeostasis in these patients by less aggressive means.

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A Non-Activating “Humanized” Anti-Cd3 Monoclonal Antibody Retains Immunosuppressive Properties in Vivo

Cited by 158 publications

References 0 publications

CD3-specific antibodies restore self-tolerance: mechanisms and clinical applications

CD3-specific antibodies restore self-tolerance: mechanisms and clinical applications

Immunotherapy of type 1 diabetes

Treatment of autoimmune hepatitis: Current and future therapies

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