MuromonabCD3

Muromonab-CD3, commonly referred to as OKT3, is a murine monoclonal antibody that targets the CD3 antigen on T lymphocytes. It was developed for immunosuppression in organ transplantation and was approved by the U.S. Food and Drug Administration in 1986 for the prevention of acute rejection.

Mechanism of action is centered on the CD3 complex of the T cell receptor. By binding to the CD3 epsilon chain, muromonab-CD3 blocks T cell receptor signaling, leading to rapid modulation and functional suppression of T cells and, in many cases, depletion of circulating CD3+ T cells. This can trigger a cytokine release reaction. The overall effect is a reduction in cellular immune responses, which helps prevent or treat organ transplant rejection, but is also associated with systemic inflammatory symptoms.

Clinical use of muromonab-CD3 has primarily been in the treatment of acute rejection episodes in kidney, heart, and liver transplantation, especially when rejection is refractory to conventional therapies such as steroids. It is not routinely used for induction or prophylaxis in most transplant protocols today due to safety concerns. Administration is via an intravenous, short course regimen tailored to the individual patient and protocol, with continuous monitoring for infusion-related reactions.

Adverse effects are significant and include cytokine release syndrome (fever, hypotension, hypoxia), severe infections due to profound immunosuppression, and hypersensitivity reactions. Its murine origin can lead to the development of human anti-mouse antibodies, limiting repeat use and potentially causing anaphylactic reactions.

Historically, muromonab-CD3 was a landmark in transplant immunology as the first monoclonal antibody approved for this purpose. Its use has declined with the advent of newer immunosuppressants and biologics that offer improved safety profiles.