Muromonab-CD3

Description

Muromonab-CD3 is a murine monoclonal antibody to the T3 antigen of human T-cells, which blocks their killing ability. It is useful in the treatment of acute allograft rejection in renal transplant patients.

Originator

Ortho (USA)

Uses

Monoclonal antibody (immunosuppressant).

brand name

Orthoclone OKT3 (Ortho Pharmaceutical);ORTHOCLONE OKT3.

General Description

Muromonab-CD3 (murine, Orthoclone-OKT3) is an unmodified mouse immunoglobulin, an IgG2a, monoclonal. It binds a glycoprotein on the surface of mature T lymphocytes. Mature T cells have, as part of the signal transduction machinery of the T-cell receptor complex, a set of three glycoproteins that are collectively called CD3. Together with the protein zeta, the CD3 molecules become phosphorylated when the T-cell receptor is bound to a peptide fragment and the major histocompatibility complex. The phosphorylated CD3 and zeta molecules transmit information into the cell, ultimately producing transcription factors that enter the nucleus and direct the T-cell activity. By binding to CD3, muromonab-CD3 prevents signal transduction into T cells.
Muromonab-CD3 blocks the function of T cells thatare involved in acute renal rejection. Hence, it is indicatedfor the treatment of acute allograft rejection in heart andliver transplant recipients resistant to standard steroidtherapies.

Mechanism of action

Muromonab-(CD3) alters the cell-mediated immune response by binding to the CD3 (cluster of differentiation antigen, T3) glycoprotein on T lymphocytes. This binding inhibits lymphocyte activation so that affected T cells cannot recognize foreign antigen and cannot participate in rejecting an organ graft.Within minutes of the first muromonab-(CD3) injection, total circulating T cells are rapidly depleted from the blood. They later reappear devoid of CD3 and antigen recognition complexes.

Clinical Use

Muromonab-(CD3) (Orthoclone OKT3) is a mouse monoclonal antibody that is a purified IgG. It is used for the prevention of acute allograft rejection in kidney and hepatic transplants and as prophylaxis in cardiac transplantation. It is also used to deplete T cells in marrow from donors before bone marrow transplantation.

Side effects

Adverse side effects include fever, pulmonary edema, vomiting, headache, and anaphylaxis. Neutralizing antibodies may develop over time and necessitate adjusting the dosage upward to compensate for the loss of therapeutic activity.