Teplizumab Overview

Introduction of Teplizumab

Teplizumab (also known as MGA031 and hOKT3γ1(Ala-Ala)) is a humanized anti-CD3 monoclonal antibody (mAb) developed at Columbia University, and was then further developed at MacroGenics, Inc. The Fc region of this antibody has been engineered to have Fc receptor non-binding (FNB) properties. This antibody has been used in clinical trials with the aim of protecting the remaining β-cells in newly diagnosed type 1 diabetes mellitus patients, but "these agents [i. e. anti-CD3-antibodies] alone do not restore normal glucose control". Eli Lilly licensed the drug back in 2007 from MacroGenics. It is in Phase-3 clinical trials for Type 1 Diabetes (T1D). One-year data from one phase III trial was disappointing.

Mechanism of Action of Teplizumab

Type 1 diabetes (T1D) is a T cell mediated autoimmune disease with selective destruction of β-cells by auto reactive CD4+ and CD8+ T lymphocytes. Other immune cells apart from CD4+ and CD8+ T cells may also play a role in development of T1D. Teplizumab is a humanized Fc-mutated anti-CD3 mAb. Teplizumab contains the binding region of the transplant rejection preventative agent OKT3, but amino acids 234 and 235 have been changed to alanine residues. As a result, this diminishes the binding to complement and Fc receptors, reducing toxicities that may be associated with murine mAb. In a mechanism that is not well understood, teplizumab reduces autoimmune destruction of pancreatic β-cells by increasing Foxp 3+, CD8+, CD25+ T-cells while maintaining CD4+ T-cells, thus leading to a reduction in the ratio of CD4+ to CD8+ cells. This shift may be the result of transforming growth factor-β and tumor necrosis factor-α mediated apoptosis of activated T-cells, immunomodulation of the T-cell receptor complex, altered trafficking, and resetting of the T-cell tolerogenic mechanisms. Furthermore, T-cells that produce interleukin-2 or interferon-γ become unresponsive, whereas T-cells that produce interleukin-4 or interleukin-10 may be stimulated. Augmentations of interleukin-2 may reverse the course of T1D and increased interferon-γ concentrations may be associated with worsened disease; therefore, reduced responsiveness of T-cells producing these mediators may improve T1D.

Fig.1 Mechanism of action of Teplizumab

Table 1. Clinical Projects of teplizumab*

What We Provide

Therapeutic Antibody

Teplizumab

We provide high-quality Teplizumab for use in WB, FC, IP, ELISA, Neut, FuncS, IF and most other immunological methods. For lab research use only, not for diagnostic, therapeutic or any in vivo human use.

Reference
* The table was excerpted from the following website
https://clinicaltrials.gov/ct2/results?cond=&term=Teplizumab

For research use only. Not intended for any clinical use.