Orthoclone

Inhibition of immunomodulatory cytokines (Fig. 1) Anti-T-cell receptor antibodies Muromonab (OKT3, Orthoclone ) binds to the CD3 complex of the T-cell receptor and induces depletion of T-lymphocytes. It is applied to prevent acute rejection of kidney, liver, and heart allografts. Rapid side effects (within 30-60 min) include a cytokine release syndrome with fever, flu-like symptoms, and shock. Late side effects include an increased risk of viral and bacterial infections and an increased incidence of lymphproliferative diseases due to immunosuppression. 

The first mouse monoclonal antibody specific for human CD3 was produced in 1979 and named orthoclone OKT3. Aside from its use in the laboratory, OKT3 became the first anti-CD3 antibody to be utilized in transplantation medicine, but its wider application was hampered by its immunogenic and mitogenic properties (reviewed in [6]). Consequently, humanized and engineered anti-CD3 antibodies were developed to circumvent these limitations (Table 1). Since T cells and the TCR are involved in many immunological diseases, it is not surprising that the application of CD3 antibodies is not restricted to the field of transplantation. For example, CD3 antibodies are tested in clinical studies of diseases such as autoimmune diabetes (type 1 diabetes), immune-mediated inflammatory arthritis and inflammatory bowel disease [7]. 

ORTHOCLONE OKT 3 Muronomab-CD3 Ortho Biotech Reversal of acute kidney transplant rejection, reversal of heart and liver transplant rejection... 

Antibodies Avastin, Bexxar, Erbitux, Herceptin, Humaspect, Humira, Mabcampath/Campath-Hl, Mabthera/ Rituxan, Mylotarg, Neutrospec, Oncoscint, Orthoclone OKT-3, Prostascint, Raptiva, Remicade, Simulect, Synagis, Xolair, Zenapax, Zevalin... 

Orthoclone OKT3 (Muromomab CD3, murine Mab directed against the T-lymphocyte surface antigen CD3)... 

Antibodies have and likely will find additional use in transplantation-related medicine. In general, cell-mediated immunological mechanisms are responsible for mediating rejection of transplanted organs. In many instances, transplant patients must be maintained on immunosuppressive drugs (e.g. some steroids and, often, the fungal metabolite cyclosporine). However, complications may arise if a rejection episode is encountered that proves unresponsive to standard immunosuppressive therapy. Orthoclone OKT-3 was the first monoclonal antibody-based product to find application in this regard. 

Goldstein, G., Overview of the development of Orthoclone OKT3 monoclonal antibody for therapeutic use in transplantation, Transplant. Proc., 19, 1, 1987. 

Orthoclone OKT3 Muromonab-GD3 Ortho Biotech, Bridgewater, NJ Anti-CD3 Transplants 1986... 

Muromonab-CD3 (Orthoclone OKT3) [Immunosuppressant/ Monoclonal Antibody] WARNING Can cause anaphylaxis monitor fluid status Uses Acute rejection following organ transplantation Action Murine Ab, blocks T-cell Fxn Dose Per protocol Adults. 5 mg/d IV for 10-14 d Peds. 0.1 mg/kg/d IV for 10-14 d Caution [C, /-] w/ Hx Szs, PRG, uncontrolled HTN Contra Murine sensitivity, fluid overload Disp Inj SE Anaphylaxis, pulm edema, fever/chills w/ 1st dose (premedicate w/ stCToid/APAP/antihistamine) Interactions t Effects W/ immunosuppressives t effects OF live virus vaccines t risk of CNS effects encephalopathy W/ indomethacin EMS Monitor for S/Sxs of Infxn monitor resp Fxn, known to... 

Sgro, C. (1995) Side-effects of a monoclonal antibody, muromonab CD3/ orthoclone OKT3 bibliographic review. Toxicology, 105, 23-29. 

Muromonab (Orthoclone OKT3 ) is a mouse monoclonal antibody that kills T lymphocytes, cells that are a part of the immune response. Muromonab, the first monoclonal antibody approved for use as a drug, is used to treat rejection of a donated kidney, liver, or... 

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. 

The first monoclonal antibody—OKT3 or Orthoclone—was designed to be immunosuppressive and to reduce the likelihood of transplant rejection. Now monoclonal antibodies are used to treat a wide range of diseases, including arthritis, certain kind of cancers, and microbial and viral infections. 

Orthoclone/OKT3 (Muromonab-CD3) CD3 Mouse IgG2 Allograft rejection 1986... 

B. Indications and use Orthoclone OKT3 is indicated for the treatment of acute allograft rejection in renal transplant patients and for the treatment of steroid-resistant acute allograft rejection in cardiac and hepatic transplant patients. 

Dosage form Each 5 ml ampule of Orthoclone OKT3 contains muromonab-CD3 5 mg in a sterile solution. 

Route of administration Orthoclone OKT3 is administered as an intravenous bolus over less than one minute. The preparation should not be administered by infusion or in conjunction with other drug solutions. 

Pharmacokinetics A rapid decrease in T-lymphocytes is observed within a few minutes after administration of Orthoclone OKT3. The volume of distribution of muromonab CD3 is approximately 6.5 liters its half-life is 18 hours. Clinical experience has demonstrated that serum levels greater than or equal to 0.8pg/ml of muromonab CD3 blocks the function of cytotoxic T cells in vitro and in vivo. Reduced T-cell clearance or low plasma... 

Drug interactions When using combinations of immunosuppressive agents, the dose of each agent, including Orthoclone OKT3, should be reduced to the lowest level compatible with an effective therapeutic response so as to reduce the potential for and severity of infections and malignant transformations. 

G. Other applications Other possible uses of Orthoclone OKT3 are for prophylaxis and treatment of acute graft-versus-host disease (as an adjunct with allogeneic bone marrow transplantation) treatment of rejection after lung transplantation prophylaxis and treatment of rejection... 

---