Teplizumab, sold under the brand nameTzield, is a humanized anti-CD3monoclonal antibody that is the first approved treatment indicated to delay the onset of stage 3type1 diabetes in people with stage 2 type1 diabetes.[5][6][7]
Teplizumab's mechanism of action involves binding toCD3 protein complexes (a molecule involved in recognising antigens and activating T cells) on the surface ofT-cells and modifying T-cell immune behaviour to reducecytotoxicity.[8] 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 activatedT effector cells. In addition, regulatory cytokines are released and regulatory T cells are expanded that may lead to the reestablishment of immune tolerance.[9][10] To avoid overly stimulating cytokine release, theFc region of this antibody has been engineered to haveFc receptor non-binding (FNB) properties.[8]
Teplizumab was developed at theUniversity of Chicago in partnership withOrtho Pharmaceutical, and was then further developed at MacroGenics, Inc.,[14][15] including a collaboration with Eli Lilly to conduct the first phase III clinical trial in early-onsettype1 diabetes.[16] After the initial Phase 3 trial conducted by Macrogenics failed to meet the primary endpoint,[17] the drug was acquired by Provention Bio, which restarted development based on subset analysis of the original trials.[18][19]
Teplizumab has been used in clinical trials with the aim of protecting the remainingβ-cells in people newly diagnosed withtype1 diabetes.[20] 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.[21]
Teplizumab has been evaluated for treatment of renal allograft rejection, for induction therapy in islet transplant recipients, and for psoriatic arthritis.[22]
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.[23]
A systematic review and meta-analysis, published in 2024, found that use of teplizumab is associated with better preservation of circulating C-peptide levels.[24]
^Chatenoud L, Bluestone JA (August 2007). "CD3-specific antibodies: a portal to the treatment of autoimmunity".Nature Reviews. Immunology.7 (8):622–32.doi:10.1038/nri2134.PMID17641665.S2CID11868182.
^Kamrul-Hasan AB, Mondal S, Nagendra L, Yadav A, Aalpona FT, Dutta D (May 2024). "Role of Teplizumab, a Humanized Anti-CD3 Monoclonal Antibody, in Managing Newly Diagnosed Type 1 Diabetes: An Updated Systematic Review and Meta-Analysis".Endocrine Practice.30 (5):431–440.doi:10.1016/j.eprac.2024.03.006.PMID38519028.
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