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Teplizumab
Monoclonal antibody From Wikipedia, the free encyclopedia
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Teplizumab, sold under the brand name Tzield, is a humanized anti-CD3 monoclonal antibody that is the first approved treatment indicated to delay the onset of stage 3 type 1 diabetes in people with stage 2 type 1 diabetes.[4][5][6]
Teplizumab's mechanism of action involves binding to CD3 protein complexes (a molecule involved in recognising antigens and activating T cells) on the surface of T-cells and modifying T-cell immune behaviour to reduce cytotoxicity.[7] This appears to involve weak agonistic activity on signaling via the T cell receptor-CD3 complex associated with the development of anergy, unresponsiveness, and/or apoptosis, particularly of unwanted activated T effector cells. In addition, regulatory cytokines are released and regulatory T cells are expanded that may lead to the reestablishment of immune tolerance. [8][9] To avoid overly stimulating cytokine release, the Fc region of this antibody has been engineered to have Fc receptor non-binding (FNB) properties.[7]
Teplizumab was approved for medical use in the United States in November 2022.[4][10] The US Food and Drug Administration (FDA) considers it to be a first-in-class medication.[11][12]
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Medical uses
Teplizumab is indicated to delay the onset of stage 3 type 1 diabetes in people aged eight years of age and older with stage 2 type 1 diabetes.[3][4]
History
Teplizumab was developed at the University of Chicago in partnership with Ortho Pharmaceutical, and was then further developed at MacroGenics, Inc.,[13][14] including a collaboration with Eli Lilly to conduct the first phase III clinical trial in early-onset type 1 diabetes.[15] After the initial Phase 3 trial conducted by Macrogenics failed to meet the primary endpoint,[16] the drug was acquired by Provention Bio, which restarted development based on subset analysis of the original trials.[17][18]
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Research
Teplizumab has been used in clinical trials with the aim of protecting the remaining β-cells in people newly diagnosed with type 1 diabetes.[19] Immunomodulatory agents such as anti-CD3-antibodies may restore normal glucose control if provided in very early stages of the disease, such as stage 2 T1DM, when there are still enough beta cells to maintain euglycemia.[20]
Teplizumab has been evaluated for treatment of renal allograft rejection, for induction therapy in islet transplant recipients, and for psoriatic arthritis.[21]
A phase II study showed that teplizumab could delay the development of diabetes in family members of type 1 diabetics showing signs of progression towards diabetes by about two years after a single treatment, renewing interest in its use as a preventive rather than therapeutic treatment in high-risk patients.[22]
A systematic review and meta-analysis, published in 2024, found that use of teplizumab is associated with better preservation of circulating C-peptide levels.[23]
References
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