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 (T1D) in people with stage 2 T1D.[3][4][5]
The
Fc region of this antibody has been engineered to have
Fc receptor non-binding (FNB) properties.[6] The mechanisms of action of teplizumab appear 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 Teff cells. In addition, regulatory cytokines are released and regulatory T cells are expanded that may lead to the reestablishment of immune tolerance [7][8]
Teplizumab is
indicated to delay the onset of stage 3 type 1 diabetes (T1D) people aged eight years of age and older with stage 2 T1D.[2][3]
History
Teplizumab was developed at the University of Chicago in partnership with Ortho Pharmaceuticals, and was then further developed at MacroGenics, Inc.,[12][13] including a collaboration with Eli Lilly to conduct the first Phase 3 clinical trial in early-onset
type 1 diabetes.[14] After the initial Phase 3 trial conducted by Macrogenics failed to meet the primary endpoint,[15] the drug was acquired by Provention Bio, which restarted development based on subset analysis of the original trials.[16][17]
Research
Teplizumab has been used in clinical trials with the aim of protecting the remaining
β-cells in newly diagnosed
type 1 diabetes patients.[18] 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.[19]
Teplizumab has been evaluated for treatment of renal allograft rejection, for induction therapy in islet transplant recipients, and for psoriatic arthritis.[20]
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.[21]
^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.