Muromonab-CD3

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Muromonab-CD3
Intravenous
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC6460H9946N1720O2043S56
Molar mass146189.98 g·mol−1
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Muromonab-CD3 (brand name Orthoclone OKT3, marketed by

organ transplants.[1][2] It is a monoclonal antibody targeted at the CD3 receptor,[3] a membrane protein on the surface of T cells. It is the first monoclonal antibody to be approved for clinical use in humans.[2]

Medical uses

Muromonab-CD3 is approved for the therapy of acute,

prophylaxis of transplant rejection, although a 1996 review has found it to be safe for that purpose.[5]

Contraindications

Except under special circumstances, the drug is contraindicated for patients with an allergy against mouse proteins, as well as patients with uncompensated

arterial hypertension or epilepsy. It should not be used during pregnancy or lactation.[2][4]

Adverse effects

Especially during the first infusion, the binding of muromonab-CD3 to CD3 can activate T cells to release

acetaminophen, and diphenhydramine are given before the infusion.[7]

Other adverse effects include

malignancies typical of immunosuppressive therapies. Neurological side effects like aseptic meningitis and encephalopathy have been observed. Possibly, they are also caused by the T cell activation.[4]

Repeated application can result in

anaphylactic reaction against the mouse protein,[2]
which may be difficult to distinguish from a CRS.

Pharmacology

T cells recognise

T cell receptor (TCR).[8]: 160  CD3 is one of the proteins that make up the TCR complex.[8]: 166  The TCR transduces the signal for the T cell to proliferate and attack the antigen.[8]
: 160 

Muromonab-CD3 is a

IgG2a antibody which was created using hybridoma technology.[9] It binds to the T cell receptor-CD3-complex (specifically the CD3 epsilon chain) on the surface of circulating T cells, initially leading to an activation,[7] but subsequently inducing the clearance of TCR complex from cell surface and apoptosis of the T cells.[10] This protects the transplant against the T cells.[2][4] When administered for transplant induction, the drug is administered daily thereafter for up to 7 days.[7]

Newer monoclonal antibodies in development with the same mechanism of action include otelixizumab (also known as TRX4), teplizumab (also known as hOKT3γ1(Ala-Ala) ), and visilizumab. They are being investigated for the treatment of other conditions like Crohn's disease, ulcerative colitis, and type 1 diabetes.

History

Muromonab-CD3 was approved by the

Committee for Proprietary Medicinal Products (CPMP, now CHMP), and a subsequent approval by the national health agencies; in Germany, for example, in 1988 by the Paul Ehrlich Institute in Frankfurt. However, the manufacturer of muromonab-CD3 has voluntarily withdrawn[11] it from the United States market in 2010 due to numerous side-effects, better-tolerated alternatives and declining usage.[12]

Society and culture

Legal status

Orthoclone OKT3 was withdrawn from the US market in 2010.[13]

Etymology

Muromonab-CD3 was developed before the WHO nomenclature of monoclonal antibodies took effect, and consequently its name does not follow this convention. Instead, it is a contraction from "murine monoclonal antibody targeting CD3".[2]

Research

It has also been investigated for use in treating T-cell acute lymphoblastic leukemia.[14]

References

  1. S2CID 8677441
    .
  2. ^
    ISBN 3-8047-1763-2
    .
  3. ^ "muromonab-CD3". Guide to Pharmacology. IUPHAR/BPS. Retrieved 21 August 2015.
  4. ^ a b c d e "Orthoclone OKT3". Professional Drug Information. Drugs.com. Archived from the original on 3 March 2016. Retrieved 3 January 2010.
  5. ^
    PMID 9188368
    .
  6. S2CID 22740065
    .
  7. ^
    PMID 19131530
    .
  8. ^
    OCLC 823736017
    .
  9. PMID 8638282
    .
  10. S2CID 31056997
    .
  11. ^ Abdi R, Martin S, Gabardi S (2009). "Immunosuppressive Strategies in Human Renal Transplantation – Induction Therapy" (PDF). Nephrology Rounds. 7 (4). Retrieved 11 November 2012.[permanent dead link]
  12. PMID 20150766
    .
  13. PMID 31643905
    .
  14. PMID 7885036
    .

Further reading
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