1. Muromonab (DB00075) Approved and Investigational Drug
Chemical Formula: C6460H9946N1720O2043S56
Molecular Weight:
Murine monoclonal antibody specific to CD3 T-cell lymphocyte antigens. More specifically it is a purified murine (mouse) monoclonal antibody, directed against the CD3 (T3) receptor on the surface of human T-cells (T-lymphocytes) cultured using the murine ascites method. Muromonab is 93% monomeric immune globulin G type 2a (IgG2a).
Indication/Usage
For treatment of organ transplant recipients, prevention of organ rejection
Pharmacodynamics
Used in organ transplant prophylaxis, Muromonab or OKT-3 binds specifically to the CD-3 complex, which is involved in antigen recognition and cell stimulation, on the surface of T lymphocytes. Immediately after administration CD-3-positive T lymphocytes are abruptly removed from circulation. It has been effective in reversing corticosteroid-resistant acute rejection in renal, liver, and cardiac transplant recipients..

2. Experimental Properties
Mechanism Of Action
Muromonab binds to the T-cell surface glycoprotein CD3 epsilon chain. It appears to kill CD-3 positive cells by inducing Fc mediated apoptosis, antibody mediated cytotoxicity and complement-dependent cytotoxicity.
Metabolism
Most likely removed by opsonization via the reticuloendothelial system when bound to T lymphocytes, or by human antimurine antibody production
Half-Life
0.8 hours (mammalian reticulocytes, in vitro)
Category
Immunologic Factors and Immunosuppressive Agents
Affected Organisms
Human and other Mammals
Drug Interactions
DB00091 (Cyclosporine): Muromonab increases the levels of cyclosporine
DB06372 (Rilonacept): results in increased immunosuppressive effects; increases the risk of infection. DB00072 (Trastuzumab): Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Experimental Properties
Melting Point- 61 °C for FAB Fragment; 71 °C for whole mAb
Hydrophobicity: 0.513
Isoelectric Point: 8.31

3. Sequence Targets Brands Heavy chain:
QVQLQQSGAELARPGASVKMSCKASGYTFTRYTMHWVKQRPGQGLEWIGYINPSRGYTNYNQKFKDKATLTTDKSSSTAYMQLSSLTSEDSAVYYCARYYDDHYCLDYWGQGTTLTVSSAKTTAPSVYPLAPVCGGTTGSSVTLGCLVKGYFPEPVTLTWNSGSLSSGVHTFPAVLQSDLYTLSSSVTVTSSTWPSQSITCNVAHPASSTKVDKKIEPRPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light chain:
QIVLTQSPAIMSASPGEKVTMTCSASSSVSYMNWYQQKSGTSPKRWIYDTSKLASGVPAHFRGSGSGTSYSLTISGMEAEDAATYYCQQWSSNPFTFGSGTKLEINRADTAPTVSIFPPSSEQLTSGGASVVCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDQDSKDSTYSMSSTLTLTKDEYERHNSYTCEATHKTSTSPIVKSFNRNEC
Targets
T-cell surface glycoprotein CD3 delta chain, T-cell surface glycoprotein CD3 epsilon chain, T-cell surface glycoprotein CD3 gamma chain, T-cell surface glycoprotein CD3 zeta chain, Low affinity immunoglobulin gamma Fc region receptor III-B, Complement C1r subcomponent, Complement C1q subcomponent subunit A, Complement C1q subcomponent subunit B, Complement C1q subcomponent subunit C, Low affinity immunoglobulin gamma Fc region receptor III-A, Complement C1s subcomponent, High affinity immunoglobulin gamma Fc receptor I, Low affinity immunoglobulin gamma Fc region receptor II-a, Low affinity immunoglobulin gamma Fc region receptor II-b, Low affinity immunoglobulin gamma Fc region receptor II-c
Brands
ORTHOCLONE OKT3 STERILE SOLUTION - Centocor Ortho Biotech, L.P.

4. ORTHOCLONE OKT3 STERILE SOLUTION
The antibody is a biochemically purified IgG2a immunoglobulin with a heavy chain of approximately 50,000 daltons and a light chain of approximately 25,000 daltons. It is directed to a glycoprotein with a molecular weight of 20,000 in the human T cell surface which is essential for T cell functions. Because it is a monoclonal antibody preparation, ORTHOCLONE OKT3 Sterile Solution is a homogeneous, reproducible antibody product with consistent, measurable reactivity to human T cells. ORTHOCLONE OKT3 (muromonab-CD3) Sterile Solution is a murine monoclonal antibody to the CD3 antigen of human T cells which functions as an immunosuppressant and prescribed to be administered intravenously.
Formulation
Each 5 mL ampule of ORTHOCLONE OKT3 Sterile Solution contains 5 mg (1 mg/mL) of muromonab-CD3 in a clear colorless solution which may contain a few fine translucent protein particles. Each ampule contains a buffered solution (pH 7.0 ± 0.5) of monobasic sodium phosphate (2.25 mg), dibasic sodium phosphate (9.0 mg), sodium chloride (43 mg), and polysorbate 80 (1.0 mg) in water for injection.
Used/Prescribed for
ORTHOCLONE OKT3 is indicated for the treatment of acute allograft rejection in renal transplant patients. ORTHOCLONE OKT3 is indicated for the treatment of steroid-resistant acute allograft rejection in cardiac and hepatic transplant patients.
Dosage
The recommended dose of ORTHOCLONE OKT3 for the treatment of acute renal, steroid-resistant cardiac, or steroid-resistant hepatic allograft rejection is 5 mg per day in a single (bolus) intravenous injection in less than one minute for 10 to 14 days. 

5. Contraindications Side- effects Drug Interactions References
Not given to patient which are hypersensitive to this or any other product of murine origin, have anti-mouse antibody titers ≥1:1000; are in (uncompensated) heart failure or in fluid overload, as evidenced by chest X-ray or a greater than 3 percent weight gain within the week prior to planned ORTHOCLONE OKT3 administration; have uncontrolled hypertension; have a history of seizures, or are predisposed to seizures;
Side- effects
ORTHOCLONE OKT3 therapy includes adverse effects: Dyspnea(21%), nausea(19%), vomiting (19%), chest pain (14%), diarrhea (14%), tremor (13%), wheezing (13%), headache (11%), tachycardia (10%), rigor (8%), and hypertension (8%), Angina, Cardiac Arrest, Fluctuation in Blood Pressure, Heart Failure, Myocardial Infarction, Shock, Thrombosis, Coma, Encephalopathy, Epilepsy, Hypotonia, Gastrointestinal Hemorrhage, Coagulation Disorder, Lymphadenopathy, Lymphopenia, Anuria, Oliguria, Apnea, Pneumonitis, Conjunctivitis, Hearing Decrease
Drug Interactions
No information provided
References