otelixizumab

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Ligands
otelixizumab

GtoPdb Ligand ID: 8458

Synonyms: ChAglyCD3 | TRX4

Comment: Otelixizumab is a chimeric humanized IgG1 monoclonal antibody targeting the CD3E component of the T cell receptor. The antibody is aglycosylated. Otelixizumab was investigated as a potential treatment for autoimmune diseases including type I diabetes [3-4].
Peptide sequences for this antibody are available from its IMGT/mAb-DB record.

No information available.

No information available.

Summary of Clinical Use
Phase 3 clinical trials evaluating otelixizumab in patients with newly diagnosed type I diabetes mellitus (autoimmune) have been completed, but results failed to meet the required study endpoints. Otelixizumab has had orphan drug designation from the US FDA since 2006, for the treatment of newly diagnosed type I diabetes mellitus. Another investigational anti-CD3E monoclonal, teplizumab (IMGT/mAb-DB ID 92, developed by Eli Lilly and MacroGenics) and which reached Phase 3 clinical trial, also reported disappointing study outcomes [5].

Summary of Clinical Use

Phase 3 clinical trials evaluating otelixizumab in patients with newly diagnosed type I diabetes mellitus (autoimmune) have been completed, but results failed to meet the required study endpoints. Otelixizumab has had orphan drug designation from the US FDA since 2006, for the treatment of newly diagnosed type I diabetes mellitus.
Another investigational anti-CD3E monoclonal, teplizumab (IMGT/mAb-DB ID 92, developed by Eli Lilly and MacroGenics) and which reached Phase 3 clinical trial, also reported disappointing study outcomes [5].

Mechanism Of Action and Pharmacodynamic Effects
Anti-CD3E antibodies such as otelixizumab, bind the target antigen but do not engage the Fc receptor on other immune system cells. This leads to a particular partial immune response with beneficial outcomes. In diabetes, antibody binding to CD3E blocks T cell function (reduces interleukin-2 production and inactivates T-helper 1 cells), reducing immune system destuction of pancreatic β-cells, whilst at the same time allowing the development of antigen tolerance [2]. A short course of treatment with otelixizumab has been shown to induce remission of overt autoimmune diabetes [4].

Mechanism Of Action and Pharmacodynamic Effects

Anti-CD3E antibodies such as otelixizumab, bind the target antigen but do not engage the Fc receptor on other immune system cells. This leads to a particular partial immune response with beneficial outcomes. In diabetes, antibody binding to CD3E blocks T cell function (reduces interleukin-2 production and inactivates T-helper 1 cells), reducing immune system destuction of pancreatic β-cells, whilst at the same time allowing the development of antigen tolerance [2]. A short course of treatment with otelixizumab has been shown to induce remission of overt autoimmune diabetes [4].