What is Teplizumab (anti-CD3 monoclonal antibody)?

From the Guidelines

Teplizumab is a CD3-directed humanized monoclonal antibody that has been approved to delay the onset of stage 3 type 1 diabetes in people 8 years of age and older with stage 2 type 1 diabetes, as evidenced by a recent study published in 2025 1. Teplizumab works by modulating the immune system to prevent it from attacking insulin-producing cells, and its use should be discussed with selected individuals who meet specific criteria, including being aged ≥8 years with stage 2 type 1 diabetes, and treatment should be administered in a setting with appropriately trained personnel. Some key points to consider when using teplizumab include:

• The medication is administered as a 14-day infusion course
• It has been shown to delay the onset of stage 3 type 1 diabetes, with a median time to diagnosis of 48.4 months in the teplizumab group compared to 24.4 months in the placebo group 1
• The presence of certain factors, such as HLA-DR4, absence of HLA-DR3, and absence of anti-zinc transporter 8 antibody, can predict response to teplizumab 1
• Common adverse reactions include transient lymphopenia (73%) and rash (36%) 1 Overall, teplizumab represents an important advancement in diabetes care, as it is the first therapy approved to specifically address the autoimmune process underlying type 1 diabetes, rather than simply treating its symptoms.

From the FDA Drug Label

Teplizumab-mzwv is a CD3-directed monoclonal antibody (humanized IgG1 kappa) that has a molecular weight of approximately 150 kilodalton (kDa) and is expressed from a recombinant Chinese hamster ovary (CHO) cell line.

Teplizumab is an anti-CD3 monoclonal antibody. It is a humanized IgG1 kappa antibody that targets the CD3 receptor on T lymphocytes. The main characteristics of Teplizumab are:

• Molecular weight: approximately 150 kilodalton (kDa)
• Expression: expressed from a recombinant Chinese hamster ovary (CHO) cell line
• Mechanism of action: binds to CD3 molecules on the surface of T cells, leading to partial agonistic signaling and deactivation of pancreatic beta cell autoreactive T lymphocytes 2

From the Research

Definition and Mechanism of Teplizumab

• Teplizumab is a humanized monoclonal antibody that targets CD3 on T cells 3, 4, 5.
• It is approved by the Food and Drug Administration to delay the onset of clinical type 1 diabetes (stage 3) in patients 8 years of age or older with preclinical (stage 2) disease 3, 4.
• The mechanism of teplizumab involves enhancing regulatory T-cell activity and promoting immune tolerance 5.

Clinical Trials and Efficacy

• Clinical trials have shown that teplizumab can delay the progression to clinical type 1 diabetes in high-risk participants 6.
• A phase 2 trial found that teplizumab delayed the diagnosis of type 1 diabetes by a median of 24 months compared to placebo 6.
• A phase 3 trial found that teplizumab preserved β-cell function in children and adolescents with newly diagnosed type 1 diabetes 3.
• Teplizumab has also been shown to induce persistent changes in the antigen-specific repertoire in individuals at risk for type 1 diabetes 7.

Safety and Adverse Events

• Common adverse events associated with teplizumab include headache, gastrointestinal symptoms, rash, lymphopenia, and mild cytokine release syndrome 3, 6.
• Teplizumab has a better side-effect profile compared to other CD3 antibodies, such as muromonab-CD3, due to its humanized nature and non-Fc-receptor-binding domain 5.