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.
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.
