Teplizumab, sold under the brand name Tzield, is a humanized anti-CD3

monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies ...

that is the first approved treatment indicated to delay the onset of stage 3

type 1 diabetes Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin (beta cells) are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar ...

(T1D) in people with stage 2 T1D. The

Fc region The fragment crystallizable region (Fc region) is the tail region of an antibody that interacts with cell surface receptors called Fc receptors and some proteins of the complement system. This property allows antibodies to activate the immune s ...

of this antibody has been engineered to have Fc receptor non-binding (FNB) properties. 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

Medical uses

Teplizumab is

indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...

to delay the onset of stage 3 type 1 diabetes (T1D) people aged eight years of age and older with stage 2 T1D.

History

Teplizumab was developed at the University of Chicago in partnership with Ortho Pharmaceuticals, and was then further developed at MacroGenics, Inc., including a collaboration with Eli Lilly to conduct the first Phase 3 clinical trial in early-onset

. After the initial Phase 3 trial conducted by Macrogenics failed to meet the primary endpoint, the drug was acquired by Provention Bio, which restarted development based on subset analysis of the original trials.

Research

Teplizumab has been used in clinical trials with the aim of protecting the remaining β-cells in newly diagnosed

patients. 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. Teplizumab has been evaluated for treatment of renal allograft rejection, for induction therapy in islet transplant recipients, and for psoriatic arthritis. 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.

References

External links

* Breakthrough therapy Monoclonal antibodies {{antineoplastic-drug-stub