Muromonab-CD3

Summary

Muromonab-CD3 is a murine IgG2a monoclonal antibody that targets the CD3 subunit of the T-cell Receptor (TCR), and was the first monoclonal antibody used to treat and prevent acute transplant rejection. First approved in 1986 for treatment of acute renal allograft rejection, OKT3 has since been widely employed to control rejection in other settings, e.g. cardiac and hepatic transplant anti-rejection regimens. The therapeutic action of muromonab-CD3 is thought to depend on both T-cell depletion and modulatory effects of antigenic stimulation via the TCR.

Significant acute toxicities associated with OKT3 administration include marked infusion-related reactions, notably hypersensitivity reactions and Cytokine Release Syndrome. Proposed mechanisms of toxicity include antibody-triggered activation of T-cells, Fc mediated systemic complement activation, and interaction with Fc-receptor expressing bystander cells. Investigations into these areas have resulted in additional engineered anti-CD3 candidate biologicals now in the development stage.

Longer term side effects reported but not unique to muromonab-CD3 include increased risk of infection due to immunosuppression and post-transplant lymphoma.

Brand Name

Orthoclone OKT3

Other Names

None

Molecular Target

CD3

Molecular Structure

murine IgG2a

Licensed Indication, Major Target Diseases

renal, cardiac, hepatic allograft rejection

Manufacturer/Distributor

Ortho Biotech

References