# Muromonab-CD3

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Pharmaceutical drug

Pharmaceutical compound

Muromonab-CD3 Monoclonal antibody Type Whole antibody Source Mouse Target CD3 Clinical data Trade names Orthoclone OKT3 AHFS/Drugs.com Consumer Drug Information MedlinePlus a605011 Routes of administration Intravenous ATC code L04AG01 (WHO) Legal status Legal status In general: ℞ (Prescription only) Identifiers CAS Number 140608-64-6 Y DrugBank DB00075 N ChemSpider none UNII JGA39ICE2V KEGG D05092 ChEMBL ChEMBL1201608 N CompTox Dashboard (EPA) DTXSID2046414 Chemical and physical data Formula C6460H9946N1720O2043S56 Molar mass 146189.98 g·mol−1 NY (what is this?) (verify)

**Muromonab-CD3** (brand name **Orthoclone OKT3**, marketed by [Janssen-Cilag](/source/Janssen-Cilag)) is an [immunosuppressant](/source/Immunosuppressant) medication given to reduce [acute rejection](/source/Acute_rejection) in people with [organ transplants](/source/Organ_transplant).[1][2] It is a [monoclonal antibody](/source/Monoclonal_antibody) targeted at the [CD3](/source/CD3_(immunology)) receptor,[3] a [membrane protein](/source/Membrane_protein) on the surface of [T cells](/source/T_cell). It is the first monoclonal antibody to be [approved](/source/Regulation_of_therapeutic_goods) for clinical use in humans.[2]

## Medical uses

Muromonab-CD3 is approved for the therapy of acute, [glucocorticoid](/source/Glucocorticoid)-resistant rejection of [allogeneic](/source/Allotransplantation) [kidney](/source/Renal_transplant), [heart](/source/Heart_transplant), and [liver transplants](/source/Liver_transplant).[4] Unlike the monoclonal antibodies [basiliximab](/source/Basiliximab) and [daclizumab](/source/Daclizumab), it is not approved for [prophylaxis](/source/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 [heart failure](/source/Heart_failure), uncontrolled [arterial hypertension](/source/Arterial_hypertension) or [epilepsy](/source/Epilepsy). It should not be used during [pregnancy](/source/Pregnancy) or [lactation](/source/Lactation).[2][4]

## Adverse effects

Especially during the first infusion, the binding of muromonab-CD3 to CD3 can activate T cells to release [cytokines](/source/Cytokines) like [tumor necrosis factor](/source/Tumor_necrosis_factor) and [interferon gamma](/source/Interferon_gamma). This [cytokine release syndrome](/source/Cytokine_release_syndrome), or CRS, includes side effects like skin reactions, [fatigue](/source/Fatigue_(medical)), [fever](/source/Fever), [chills](/source/Chills), [myalgia](/source/Myalgia), [headaches](/source/Headaches), [nausea](/source/Nausea) and [diarrhea](/source/Diarrhea),[6] and could lead to life-threatening conditions like [apnoea](/source/Apnoea), [cardiac arrest](/source/Cardiac_arrest), and [flash pulmonary edema](/source/Flash_pulmonary_edema).[4] To minimize the risk of CRS and to offset some of the minor side effects patient experience, [glucocorticoids](/source/Glucocorticoid) (such as [methylprednisolone](/source/Methylprednisolone)), [acetaminophen](/source/Acetaminophen), and [diphenhydramine](/source/Diphenhydramine) are given before the infusion.[7]

Other adverse effects include [leucopenia](/source/Leucopenia), as well as an increased risk for severe infections and [malignancies](/source/Malignancies) typical of immunosuppressive therapies. [Neurological](/source/Neurology) side effects like [aseptic meningitis](/source/Aseptic_meningitis) and [encephalopathy](/source/Encephalopathy) have been observed. Possibly, they are also caused by the T cell activation.[4]

Repeated application can result in [tachyphylaxis](/source/Tachyphylaxis) (reduced effectiveness) due to the formation of anti-mouse antibodies in the patient, which accelerates elimination of the drug. It can also lead to an [anaphylactic reaction](/source/Anaphylactic_reaction) against the mouse protein,[2] which may be difficult to distinguish from a CRS.

## Pharmacology

T cells recognise [antigens](/source/Antigen) primarily via the [T cell receptor](/source/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](/source/Cell_proliferation) and attack the antigen.[8]: 160

Muromonab-CD3 is a [murine](/source/Murine) (mouse) monoclonal [IgG2a](/source/IgG2) antibody which was created using [hybridoma technology](/source/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](/source/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](/source/Otelixizumab) (also known as TRX4), [teplizumab](/source/Teplizumab) (also known as hOKT3γ1(Ala-Ala) ), [visilizumab](/source/Visilizumab) and [foralumab](/source/Foralumab). They are being investigated for the treatment of other conditions like [Crohn's disease](/source/Crohn's_disease), [ulcerative colitis](/source/Ulcerative_colitis), and [type 1 diabetes](/source/Type_1_diabetes).

## History

Muromonab-CD3 was approved by the [U.S. Food and Drug Administration](/source/U.S._Food_and_Drug_Administration) (FDA) in 1986,[5] making it the first monoclonal antibody to be approved anywhere as a drug for humans. In the [European Communities](/source/European_Communities), it is the first drug to be approved under the [directive](/source/Directive_(European_Union)) 87/22/EWG, a precursor of the [European Medicines Agency](/source/European_Medicines_Agency) (EMA) centralised approval system in the European Union. This process included an assessment by the [Committee for Proprietary Medicinal Products](/source/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](/source/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](/source/World_Health_Organization) [nomenclature of monoclonal antibodies](/source/Nomenclature_of_monoclonal_antibodies) took effect, and consequently its name does not follow this convention. Instead, it is a contraction from "*mur*ine *mon*oclonal *a*nti*b*ody targeting *CD3*".[2]

## Research

It has also been investigated for use in treating [T-cell acute lymphoblastic leukemia](/source/T-lymphoblastic_leukemia%2Flymphoma).[14]

## References

1. **[^](#cite_ref-pmid12588325_1-0)** Midtvedt K, Fauchald P, Lien B, Hartmann A, Albrechtsen D, Bjerkely BL, et al. (February 2003). "Individualized T cell monitored administration of ATG versus OKT3 in steroid-resistant kidney graft rejection". *Clinical Transplantation*. **17** (1): 69–74. [doi](/source/Doi_(identifier)):[10.1034/j.1399-0012.2003.02105.x](https://doi.org/10.1034%2Fj.1399-0012.2003.02105.x). [PMID](/source/PMID_(identifier)) [12588325](https://pubmed.ncbi.nlm.nih.gov/12588325). [S2CID](/source/S2CID_(identifier)) [8677441](https://api.semanticscholar.org/CorpusID:8677441).

1. ^ [***a***](#cite_ref-Mutschler_2-0) [***b***](#cite_ref-Mutschler_2-1) [***c***](#cite_ref-Mutschler_2-2) [***d***](#cite_ref-Mutschler_2-3) [***e***](#cite_ref-Mutschler_2-4) [***f***](#cite_ref-Mutschler_2-5) Mutschler E, Geisslinger G, Kroemer HK, Schäfer-Korting M (2001). *Arzneimittelwirkungen* (in German) (8 ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. p. 937. [ISBN](/source/ISBN_(identifier)) [3-8047-1763-2](https://en.wikipedia.org/wiki/Special:BookSources/3-8047-1763-2).

1. **[^](#cite_ref-3)** ["muromonab-CD3"](http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6889). *Guide to Pharmacology*. IUPHAR/BPS. Retrieved 21 August 2015.

1. ^ [***a***](#cite_ref-DrugsCom_4-0) [***b***](#cite_ref-DrugsCom_4-1) [***c***](#cite_ref-DrugsCom_4-2) [***d***](#cite_ref-DrugsCom_4-3) [***e***](#cite_ref-DrugsCom_4-4) ["Orthoclone OKT3"](https://web.archive.org/web/20160303193952/http://www.drugs.com/mmx/orthoclone-okt3.html). *Professional Drug Information*. Drugs.com. Archived from [the original](https://www.drugs.com/mmx/orthoclone-okt3.html) on 3 March 2016. Retrieved 3 January 2010.

1. ^ [***a***](#cite_ref-Smith_5-0) [***b***](#cite_ref-Smith_5-1) Smith SL (September 1996). "Ten years of Orthoclone OKT3 (muromonab-CD3): a review". *Journal of Transplant Coordination*. **6** (3): 109–119, quiz 119–1. [doi](/source/Doi_(identifier)):[10.7182/prtr.1.6.3.8145l3u185493182](https://doi.org/10.7182%2Fprtr.1.6.3.8145l3u185493182) (inactive 1 July 2025). [PMID](/source/PMID_(identifier)) [9188368](https://pubmed.ncbi.nlm.nih.gov/9188368).{{[cite journal](https://en.wikipedia.org/wiki/Template:Cite_journal)}}: CS1 maint: DOI inactive as of July 2025 ([link](https://en.wikipedia.org/wiki/Category:CS1_maint:_DOI_inactive_as_of_July_2025))

1. **[^](#cite_ref-6)** Abramowicz D, Schandene L, Goldman M, Crusiaux A, Vereerstraeten P, De Pauw L, et al. (April 1989). ["Release of tumor necrosis factor, interleukin-2, and gamma-interferon in serum after injection of OKT3 monoclonal antibody in kidney transplant recipients"](https://doi.org/10.1097%2F00007890-198904000-00008). *Transplantation*. **47** (4): 606–608. [doi](/source/Doi_(identifier)):[10.1097/00007890-198904000-00008](https://doi.org/10.1097%2F00007890-198904000-00008). [PMID](/source/PMID_(identifier)) [2523100](https://pubmed.ncbi.nlm.nih.gov/2523100). [S2CID](/source/S2CID_(identifier)) [22740065](https://api.semanticscholar.org/CorpusID:22740065).

1. ^ [***a***](#cite_ref-Bhorade2009_7-0) [***b***](#cite_ref-Bhorade2009_7-1) [***c***](#cite_ref-Bhorade2009_7-2) Bhorade SM, Stern E (January 2009). "Immunosuppression for lung transplantation". *Proceedings of the American Thoracic Society*. **6** (1): 47–53. [doi](/source/Doi_(identifier)):[10.1513/pats.200808-096go](https://doi.org/10.1513%2Fpats.200808-096go). [PMID](/source/PMID_(identifier)) [19131530](https://pubmed.ncbi.nlm.nih.gov/19131530).

1. ^ [***a***](#cite_ref-Rich2013_8-0) [***b***](#cite_ref-Rich2013_8-1) [***c***](#cite_ref-Rich2013_8-2) Rich R (2013). [*Clinical immunology : principles and practice*](https://www.sciencedirect.com/book/9780723436911/clinical-immunology) (4th ed.). London: Elsevier. [ISBN](/source/ISBN_(identifier)) [978-0-7234-3710-9](https://en.wikipedia.org/wiki/Special:BookSources/978-0-7234-3710-9). [OCLC](/source/OCLC_(identifier)) [823736017](https://search.worldcat.org/oclc/823736017).

1. **[^](#cite_ref-9)** Sgro C (December 1995). "Side-effects of a monoclonal antibody, muromonab CD3/orthoclone OKT3: bibliographic review". *Toxicology*. Immunotoxicology Papers presented at the Third Summer School in Immunotoxicology. **105** (1): 23–29. [Bibcode](/source/Bibcode_(identifier)):[1995Toxgy.105...23S](https://ui.adsabs.harvard.edu/abs/1995Toxgy.105...23S). [doi](/source/Doi_(identifier)):[10.1016/0300-483X(95)03123-W](https://doi.org/10.1016%2F0300-483X%2895%2903123-W). [PMID](/source/PMID_(identifier)) [8638282](https://pubmed.ncbi.nlm.nih.gov/8638282).

1. **[^](#cite_ref-10)** Benekli M, Hahn T, Williams BT, Cooper M, Roy HN, Wallace P, et al. (September 2006). ["Muromonab-CD3 (Orthoclone OKT3), methylprednisolone and cyclosporine for acute graft-versus-host disease prophylaxis in allogeneic bone marrow transplantation"](https://doi.org/10.1038%2Fsj.bmt.1705450). *Bone Marrow Transplantation*. **38** (5): 365–370. [doi](/source/Doi_(identifier)):[10.1038/sj.bmt.1705450](https://doi.org/10.1038%2Fsj.bmt.1705450). [PMID](/source/PMID_(identifier)) [16862164](https://pubmed.ncbi.nlm.nih.gov/16862164). [S2CID](/source/S2CID_(identifier)) [31056997](https://api.semanticscholar.org/CorpusID:31056997).

1. **[^](#cite_ref-11)** Abdi R, Martin S, Gabardi S (2009). ["Immunosuppressive Strategies in Human Renal Transplantation – Induction Therapy"](https://web.archive.org/web/20200526092359/http://www.nephrologyrounds.org/crus/304-072.pdf) (PDF). *Nephrology Rounds*. **7** (4). Archived from [the original](http://www.nephrologyrounds.org/crus/304-072.pdf) (PDF) on 26 May 2020. Retrieved 11 November 2012.

1. **[^](#cite_ref-12)** Mahmud N, Klipa D, Ahsan N (2010). ["Antibody immunosuppressive therapy in solid-organ transplant: Part I"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2840233). *mAbs*. **2** (2): 148–156. [doi](/source/Doi_(identifier)):[10.4161/mabs.2.2.11159](https://doi.org/10.4161%2Fmabs.2.2.11159). [PMC](/source/PMC_(identifier)) [2840233](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2840233). [PMID](/source/PMID_(identifier)) [20150766](https://pubmed.ncbi.nlm.nih.gov/20150766).

1. **[^](#cite_ref-13)** ["Drug Record: Muromonab-CD3"](https://www.ncbi.nlm.nih.gov/books/NBK548590/). [*Livertox: Clinical and Research Information on Drug-Induced Liver Injury*](https://www.ncbi.nlm.nih.gov/books/NBK547852/). National Institute of Diabetes and Digestive and Kidney Diseases. 2012. [PMID](/source/PMID_(identifier)) [31643905](https://pubmed.ncbi.nlm.nih.gov/31643905).

1. **[^](#cite_ref-pmid7885036_14-0)** Gramatzki M, Burger R, Strobel G, Trautmann U, Bartram CR, Helm G, et al. (March 1995). "Therapy with OKT3 monoclonal antibody in refractory T cell acute lymphoblastic leukemia induces interleukin-2 responsiveness". *Leukemia*. **9** (3): 382–390. [PMID](/source/PMID_(identifier)) [7885036](https://pubmed.ncbi.nlm.nih.gov/7885036).

## Further reading

- Todd PA, Brogden RN (June 1989). "Muromonab CD3. A review of its pharmacology and therapeutic potential". *Drugs*. **37** (6): 871–99. [doi](/source/Doi_(identifier)):[10.2165/00003495-198937060-00004](https://doi.org/10.2165%2F00003495-198937060-00004). [PMID](/source/PMID_(identifier)) [2503348](https://pubmed.ncbi.nlm.nih.gov/2503348). [S2CID](/source/S2CID_(identifier)) [30478429](https://api.semanticscholar.org/CorpusID:30478429).

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Adapted from the Wikipedia article [Muromonab-CD3](https://en.wikipedia.org/wiki/Muromonab-CD3) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Muromonab-CD3?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.