Muromonab CD3

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Muromonab CD3
Mass / length primary structure 146.2  kDa
Identifier
External IDs
Drug information
ATC code L04 AA02
DrugBank DB00075
Drug class Immunosuppressants , Monoclonal Antibodies

Muromonab-CD3 (trade name Orthoclone OKT3 ® ; manufacturer Janssen-Cilag ) is a murine therapeutic monoclonal antibody against the CD3 receptor , a membrane protein on the cell surface of T lymphocytes . The antibody can be used in the immunosuppressive treatment of an acute rejection reaction after organ transplantation . Muromonab-CD3 was the first monoclonal antibody worldwide to be approved for therapeutic purposes in 1986.

Clinical information

Muromonab-CD3 is approved for the treatment of acute, steroid-resistant rejection reactions following allogeneic kidney , heart and liver transplants . In contrast to other antibodies such as basiliximab or daclizumab, the prophylactic administration of muromonab-CD3 prior to transplantation is not indicated for muromonab-CD3 due to the expected considerable side effects.

Muromonab-CD3 is given as an intravenous injection. The usual dose for adults is 5 mg per day.

Contraindications (contraindications)

Muromonab-CD3 must not be administered if there is known hypersensitivity to the active substance. The drug should not be used even if antibodies (titer ≥ 1: 1000) against mouse IgG are present. A heart failure , uncontrolled hypertension or previous seizures are also contraindications. It is also not indicated during pregnancy and breastfeeding.

Adverse effects (side effects)

The administration of Muromonab-CD3 can lead to a number of side effects , some of them severe . The first infusion in particular can lead to a massive release of cytokines , in particular tumor necrosis factor -α and interferon -γ. Such a cytokine release syndrome is associated, among other things, with a feeling of weakness and a skin reaction with fever, chills, nausea and muscle and joint pain. In severe cases, circulatory collapse and life-threatening respiratory and cardiac arrests can occur. To avoid this, glucocorticoids are given before the infusion to reduce or prevent such a reaction. Even with anaphylactic reactions can be expected; these cannot always be distinguished from cytokine release syndrome.

Neuropsychiatric reactions such as seizures, aseptic meningitis or encephalopathy are also attributed to T-cell activation and cytokine release. Due to the strong immunosuppressive effect, more and more severe infections must be expected. The patients also have an increased risk of malignant neoplasms.

Since Muromonab-CD3 is an antibody from the mouse, the formation of human anti-mouse antibodies is induced in the human body after administration . Such antibodies can prevent the successful reuse of Muromonab-CD3 because they can neutralize the active substance; the elimination is also accelerated by such human anti-mouse antibodies.

Pharmacological properties

Mechanism of action (pharmacodynamics)

Muromonab-CD3 binds to the epsilon protein subunit of the CD3 receptor . The CD3 receptor is associated with the T cell receptor on the cell surface of T lymphocytes and interacts with it during signal transduction and activation of T lymphocytes. The binding of Muromonab-CD3 to CD3 first activates the cells for a short time, but later blocks the function of the T cells and induces apoptosis . This suppresses the rejection reaction against the transplanted organ. After the end of treatment with the antibody, the function of the CD3-positive T cells should normalize within a week.

Newer, better tolerated, but not yet approved antibodies with the same mechanism of action are teplizumab and visilizumab .

Other Information

Chemical information

Muromonab-CD3 is a mouse monoclonal antibody of the IgG 2a type . The antibody was identified using hybridoma technology and purified biochemically from ascites fluid. The finished drug also contains polysorbate 80, sodium chloride, disodium hydrogen phosphate, sodium dihydrogen phosphate and water for injection purposes as auxiliary substances .

History

ORTHOCLONE OKT3 was in the United States of the 1986 Food and Drug Administration (FDA) approved . Orthoclone OKT3 was the first drug based on a monoclonal antibody worldwide to receive approval. In the European Community, Orthoclone OKT3 was not only the first approved monoclonal antibody, but also the first medicinal product to be approved under a new consultation procedure for innovative biotechnological medicinal products based on Directive 87/22 / EEC, a forerunner to the centralized procedure. The drug was assessed by the European Committee for Medicinal Products (CPMP), the forerunner of the CHMP ; the approval was granted at the time by national authorities, for Germany on July 18, 1988 the Paul Ehrlich Institute .

See also

swell

  1. ↑ a b c Specialist information Orthoclone OKT® 3 from the Swiss Medicines Compendium , accessed on July 11, 2008.
  2. ↑ D. Abramowicz, L. Schandene, M. Goldman, A. Crusiaux, P. Vereerstraeren, L. De Pauw, J. Wybran, P. Kinnaert, E. Dupont, C. Toussaint: Release of tumor necrosis factor, interleukin- 2, and gamma-interferon in serum after injection of OKT3 monoclonal antibody in kidney transplant recipients. In: transplant. (1989) Vol. 47, PMID 2523100 , pp. 606-608.
  3. ↑ L. Chatenoud , JA Bluestone: CD3-specific antibodies: a portal to the treatment of autoimmunity. In: Nat Rev Immunol . 2007 Aug; 7 (8), PMID 17641665 , pp. 622-632.

literature

  • Angelika Vollmar, Theodor Dingermann: Immunology: Basics and active ingredients. Knowledge Verl.-Ges., Stuttgart 2005, ISBN 3-8047-2189-3 , pp. 332-334.