muromonab cd3


Summary: Anti-CD3 monoclonal antibody that exerts immunosuppressive effects by inducing peripheral T-cell depletion and modulation of the T-cell receptor complex (CD3/Ti).

Top Publications

  1. Sanchez E, Marubashi S, Jung G, Levy M, Goldstein R, Molmenti E, et al. De novo tumors after liver transplantation: a single-institution experience. Liver Transpl. 2002;8:285-91 pubmed
    ..The risk for development was not enough to preclude transplantation. We found that tumors developed in chronological fashion. Therefore, directed surveillance, patient education, and early detection may facilitate earlier treatment. ..
  2. Mori A, Kaminuma O, Miyazawa K, Ogawa K, Okudaira H, Akiyama K. p38 mitogen-activated protein kinase regulates human T cell IL-5 synthesis. J Immunol. 1999;163:4763-71 pubmed
    ..Selective control of IL-5 synthesis will provide a novel treatment devoid of generalized immune suppression for bronchial asthma and atopic dermatitis that are characterized by eosinophilic inflammation. ..
  3. Miyara M, Wing K, Sakaguchi S. Therapeutic approaches to allergy and autoimmunity based on FoxP3+ regulatory T-cell activation and expansion. J Allergy Clin Immunol. 2009;123:749-55; quiz 756-7 pubmed publisher
    ..The feasibility of such Treg cell-based therapeutic strategies is discussed based on recent advances in our understanding of the molecular and cellular basis of Treg cell development and function. ..
  4. Bilinska Z, Grzybowski J, Szajewski T, Stepinska J, Michalak E, Walczak E, et al. Active lymphocytic myocarditis treated with murine OKT3 monoclonal antibody in a patient presenting with intractable ventricular tachycardia. Tex Heart Inst J. 2002;29:113-7 pubmed
    ..pylori. We discuss the possibility of a causal relationship between H. pylori infection and autoimmune myocarditis. ..
  5. Bisikirska B, Colgan J, Luban J, Bluestone J, Herold K. TCR stimulation with modified anti-CD3 mAb expands CD8+ T cell population and induces CD8+CD25+ Tregs. J Clin Invest. 2005;115:2904-13 pubmed
    ..Foxp3 was also induced on CD8+ T cells in patients during mAb treatment, which suggests a potential mechanism of the anti-CD3 mAb immune modulatory effects involving induction of a subset of regulatory CD8+ T cells. ..
  6. Mohr D, Goodkin D, Islar J, Hauser S, Genain C. Treatment of depression is associated with suppression of nonspecific and antigen-specific T(H)1 responses in multiple sclerosis. Arch Neurol. 2001;58:1081-6 pubmed
    ..Thus, treatment of depression may provide a novel disease-modifying therapeutic strategy as well as a symptomatic treatment for patients with MS. ..
  7. Teyssier J, Rousset F, Garcia E, Cornillet P, Laubriet A. Upregulation of the netrin receptor (DCC) gene during activation of b lymphocytes and modulation by interleukins. Biochem Biophys Res Commun. 2001;283:1031-6 pubmed
    ..In contrast no effect has been detected after activation of T cells by anti-CD3. These data suggest that the DCC encoded netrin receptor is involved in B cell immunopoiesis. ..
  8. Engedal N, Gjevik T, Blomhoff R, Blomhoff H. All-trans retinoic acid stimulates IL-2-mediated proliferation of human T lymphocytes: early induction of cyclin D3. J Immunol. 2006;177:2851-61 pubmed
    ..In conclusion, our results indicate that RA, via RAR, stimulates IL-2-induced signaling in a JAK-dependent manner to enhance cyclin D3 expression and thereby promote T cell proliferation. ..
  9. Ko S, Dahlke M, Lauth O, Jager M, Deiwick A, Dinkel A, et al. Bone marrow aplasia induced by passenger leukocytes from heart allografts. Exp Hematol. 2001;29:339-44 pubmed
    ..The study shows that, under defined conditions, allogeneic passenger leukocytes in a heart graft can have a profound effect on the recipient's immune system and bone marrow. ..

More Information


  1. Crespo Leiro M, Alonso Pulpon L, Arizón J, Almenar L, Delgado J, Palomo J, et al. Influence of induction therapy, immunosuppressive regimen and anti-viral prophylaxis on development of lymphomas after heart transplantation: data from the Spanish Post-Heart Transplant Tumour Registry. J Heart Lung Transplant. 2007;26:1105-9 pubmed
    ..Induction therapies with ATG or OKT3 do or do not increase the risk of lymphoma depending on whether anti-viral prophylaxis with acyclovir or ganciclovir is or is not employed, respectively. ..
  2. Lord G, Matarese G, Howard J, Bloom S, Lechler R. Leptin inhibits the anti-CD3-driven proliferation of peripheral blood T cells but enhances the production of proinflammatory cytokines. J Leukoc Biol. 2002;72:330-8 pubmed
    ..However, despite this inhibition of proliferation, the production of proinflammatory cytokines is significantly enhanced by leptin. The findings demonstrated here show further complexity in the actions of leptin on the immune system. ..
  3. Ohira M, Ishiyama K, Tanaka Y, Doskali M, Igarashi Y, Tashiro H, et al. Adoptive immunotherapy with liver allograft-derived lymphocytes induces anti-HCV activity after liver transplantation in humans and humanized mice. J Clin Invest. 2009;119:3226-35 pubmed publisher
    ..Thus, our study presents what we believe to be a novel paradigm for the inhibition of HCV replication in HCV-infected liver transplantation recipients. ..
  4. Woodle E, Xu D, Zivin R, Auger J, Charette J, O Laughlin R, et al. Phase I trial of a humanized, Fc receptor nonbinding OKT3 antibody, huOKT3gamma1(Ala-Ala) in the treatment of acute renal allograft rejection. Transplantation. 1999;68:608-16 pubmed
    ..These results support the conduct of additional clinical trials with the huOKT3gamma1(Ala-Ala) antibody. ..
  5. Kang M, Yun S, Won J. Rosmarinic acid inhibits Ca2+-dependent pathways of T-cell antigen receptor-mediated signaling by inhibiting the PLC-gamma 1 and Itk activity. Blood. 2003;101:3534-42 pubmed
  6. Albert M, Schuster F, Peters C, Schulze S, Pontz B, Muntau A, et al. T-cell-depleted peripheral blood stem cell transplantation for alpha-mannosidosis. Bone Marrow Transplant. 2003;32:443-6 pubmed
    ..The pattern of urinary oligosaccharides has returned to almost normal. CD34-positive-selected PBSCT is a feasible option to reduce risk for GVHD for these patients. ..
  7. Söderström T, Poukkula M, Holmström T, Heiskanen K, Eriksson J. Mitogen-activated protein kinase/extracellular signal-regulated kinase signaling in activated T cells abrogates TRAIL-induced apoptosis upstream of the mitochondrial amplification loop and caspase-8. J Immunol. 2002;169:2851-60 pubmed
    ..The results of this study show clearly that MAPK/ERK also participates in the inhibition of TRAIL-induced apoptosis after T cell activation. ..
  8. Heifets M, Saeed M, Parikh M, Sierka D, Kumar M. Induction immunosuppression in kidney transplant recipients older than 60 years of age : safety and efficacy of ATGAM, OKT3 and Simulect. Drugs Aging. 2004;21:747-56 pubmed
    ..transplant recipients receiving lymphocyte immune globulin, equine antithymocyte globulin (ATGAM) [n = 29]; muromonab CD3 (OKT3) [n = 45]; basiliximab (Simulect) with corticosteroid maintenance [n = 40]; and Simulect without ..
  9. van Praag R, Prins J, Roos M, Schellekens P, ten Berge I, Yong S, et al. OKT3 and IL-2 treatment for purging of the latent HIV-1 reservoir in vivo results in selective long-lasting CD4+ T cell depletion. J Clin Immunol. 2001;21:218-26 pubmed
    ..CD8+ cells were also depleted in the blood, but less severely in lymph nodes, and returned to baseline levels within several weeks. ..
  10. Chatenoud L, Bach J. Resetting the functional capacity of regulatory T cells: a novel immunotherapeutic strategy to promote immune tolerance. Expert Opin Biol Ther. 2005;5 Suppl 1:S73-81 pubmed
  11. Takahashi I, Kosaka H, Oritani K, Heath W, Ishikawa J, Okajima Y, et al. A new IFN-like cytokine, limitin, modulates the immune response without influencing thymocyte development. J Immunol. 2001;167:3156-63 pubmed
  12. Scornik J, Clapp W, Patton P, Van der Werf W, Hemming A, Reed A, et al. Outcome of kidney transplants in patients known to be flow cytometry crossmatch positive. Transplantation. 2001;71:1098-102 pubmed
    ..The risk seems to be due to donor-specific memory rather than to a direct effect of the antibodies. The results indicate that flow cytometry provides useful information to assess donor-recipient compatibility. ..
  13. Kirk A. Induction immunosuppression. Transplantation. 2006;82:593-602 pubmed
    ..Clinical trials investigating induction regimens will be evaluated, and an individualized approach to the use of induction immunosuppressants will be presented. ..
  14. Fraile P, Garcia Cosmes P, Martin P, García Bernalt V, Tabernero J. Non-skin solid tumors as a cause of morbidity and mortality after liver transplantation. Transplant Proc. 2009;41:2433-4 pubmed publisher
    ..The incidence of nonskin tumors was lower than that in published series, probably because of routine screening of patients while on the waiting list and in transplant recipients with functioning grafts. ..
  15. Ablamunits V, Bisikirska B, Herold K. Acquisition of regulatory function by human CD8(+) T cells treated with anti-CD3 antibody requires TNF. Eur J Immunol. 2010;40:2891-901 pubmed publisher
    ..These studies have identified a novel mechanism of immune regulation by anti-CD3 mAb and markers that may be used to track inducible CD8(+) Treg in settings such as chronic inflammation or immune therapy. ..
  16. Li B, Wang H, Dai J, Ji J, Qian W, Zhang D, et al. Construction and characterization of a humanized anti-human CD3 monoclonal antibody 12F6 with effective immunoregulation functions. Immunology. 2005;116:487-98 pubmed
  17. Dhanireddy K, Xu H, Mannon R, Hale D, Kirk A. The clinical application of monoclonal antibody therapies in renal transplantation. Expert Opin Emerg Drugs. 2004;9:23-37 pubmed
    ..It will provide a general overview of this class of agents and their mechanisms of action. Standard therapies and potential new applications will be described. ..
  18. Sabapathy K, Hu Y, Kallunki T, Schreiber M, David J, Jochum W, et al. JNK2 is required for efficient T-cell activation and apoptosis but not for normal lymphocyte development. Curr Biol. 1999;9:116-25 pubmed
    ..JNK2 is not required for activation-induced cell death of mature T cells. ..
  19. Vanhove B. [Monoclonal antibodies in organ transplantation]. Med Sci (Paris). 2009;25:1121-5 pubmed publisher
  20. Biller H, Bade B, Matthys H, Luttmann W, Virchow J. Interferon-gamma secretion of peripheral blood CD8+ T lymphocytes in patients with bronchial asthma: in vitro stimulus determines cytokine production. Clin Exp Immunol. 2001;126:199-205 pubmed
    ..These findings have implications for further studies investigating cytokine production of inflammatory cells in vitro. ..
  21. Uchiyama H, Yanaga K, Kishihara K, Nomoto K, Sugimachi K. Increased urinary nitrate excretion associated with hepatic allograft rejection in experimental rat models and clinical cases. Transpl Int. 2000;13:260-5 pubmed
    ..These results suggest that urinary nitrate excretion is a useful indicator for the surveillance of graft rejection and the monitoring of therapeutic effects of antirejection treatments. ..
  22. Wood G, Holladay F, Turner T, Wang Y, Chiga M. A pilot study of autologous cancer cell vaccination and cellular immunotherapy using anti-CD3 stimulated lymphocytes in patients with recurrent grade III/IV astrocytoma. J Neurooncol. 2000;48:113-20 pubmed
    ..Additional studies also will be required to determine the underlying immunological mechanisms. ..
  23. Lopez R, Xu S, Guo B, Negrin R, Waller E. CD2-mediated IL-12-dependent signals render human gamma delta-T cells resistant to mitogen-induced apoptosis, permitting the large-scale ex vivo expansion of functionally distinct lymphocytes: implications for the development of adoptive immunotherap. Blood. 2000;96:3827-37 pubmed
    ..Blood. 2000;96:3827-3837) ..
  24. Machado P, Tedesco H, Silva R, Pacheco Silva A, Medina J. Use of reduced dose of OKT3 (2.5 mg) after renal transplantation. Transplant Proc. 2002;34:104 pubmed
  25. Kalil R, Hudson S, Gaston R. Determinants of cardiovascular mortality after renal transplantation: a role for cytomegalovirus?. Am J Transplant. 2003;3:79-81 pubmed
    ..Risk of cardiovascular death was greatest (p < 0.05) in patients with diabetes, advancing age, and CMV seropositivity. In renal transplant recipients, infection with CMV increases risk of death as a result of cardiovascular causes. ..
  26. Bostik P, Mayne A, Villinger F, Greenberg K, Powell J, Ansari A. Relative resistance in the development of T cell anergy in CD4+ T cells from simian immunodeficiency virus disease-resistant sooty mangabeys. J Immunol. 2001;166:506-16 pubmed
    ..This function of CD4(+) T cells from SM may contribute to the resistance of this species to SIV-induced disease...
  27. Cohen S. Current immunosuppression in liver transplantation. Am J Ther. 2002;9:119-25 pubmed
    ..The single most important factor in this progression has been the development of effective immunosuppressive regimens. This article will outline the various immunosuppressive agents used in liver transplantation. ..
  28. Zhang R, Haverich A, Struber M, Simon A, Bara C. Delayed onset of cardiac allograft vasculopathy by induction therapy using anti-thymocyte globulin. J Heart Lung Transplant. 2008;27:603-9 pubmed publisher
    ..In contrast, OKT3 failed to show such benefit. However, induction therapy with either ATG or OKT3 did not exhibit a significant beneficial effect on long-term patient survival. ..
  29. Meier Kriesche H, Arndorfer J, Kaplan B. Association of antibody induction with short- and long-term cause-specific mortality in renal transplant recipients. J Am Soc Nephrol. 2002;13:769-72 pubmed
    ..In addition, ABI was associated with a significant risk for long-term malignancy-related death. The risk of ABI should be taken in context with potential benefits of this therapy. ..
  30. Herold K, Gitelman S, Greenbaum C, Puck J, Hagopian W, Gottlieb P, et al. Treatment of patients with new onset Type 1 diabetes with a single course of anti-CD3 mAb Teplizumab preserves insulin production for up to 5 years. Clin Immunol. 2009;132:166-73 pubmed publisher
    ..The drug may marginate rather than deplete T cells. C-peptide levels may remain detectable up to 5 years after treatment. ..
  31. Chatenoud L. [One step towards restoration of self-tolerance in human autoimmune diseases]. Med Sci (Paris). 2007;23:167-71 pubmed
    ..CD3 antibodies may represent a new category of drugs affording a real cure for autoimmunity namely, inhibiting the pathogenic immune response while preserving the host reactivity to unrelated antigens. ..
  32. Genberg H, Kumlien G, Shanwell A, Tyden G. Refractory acute renal allograft rejection successfully treated with photopheresis. Transplant Proc. 2005;37:3288-9 pubmed
    ..We are presently designing a prospective randomized study to further evaluate the effect of photopheresis after renal transplantation. ..
  33. Herold K, Gitelman S, Masharani U, Hagopian W, Bisikirska B, Donaldson D, et al. A single course of anti-CD3 monoclonal antibody hOKT3gamma1(Ala-Ala) results in improvement in C-peptide responses and clinical parameters for at least 2 years after onset of type 1 diabetes. Diabetes. 2005;54:1763-9 pubmed
  34. Tang S, Lai K. Quiz page. Posttransplantation lymphoproliferative disorder (PTLD) involving the brain and the allograft. Am J Kidney Dis. 2005;45:A55, e61-2 pubmed
  35. Hirokawa M, Miura I, Sawada K. [GVHD]. Nihon Rinsho. 2004;62 Suppl 5:478-81 pubmed
  36. Galante N, Camara N, Kallas E, Salomao R, Pacheco Silva A. Modulation of peripheral blood T-lymphocytes in kidney transplant recipients treated with low dose OKT3 therapy. Immunol Lett. 2004;91:75-7 pubmed
    ..In conclusion, low dose OKT3 was effective in treating severe allograft rejection by inducing a sustained TCR/CD3 down modulation without long-lasting T cell depletion. ..
  37. Parikh C, Klem P, Wong C, Yalavarthy R, Chan L. Obesity as an independent predictor of posttransplant diabetes mellitus. Transplant Proc. 2003;35:2922-6 pubmed
    ..Obese patients should be treated with a less diabetogenic immunosuppressive regimen and be counseled to lose weight before transplant. ..
  38. Zhang Z, Elly C, Qiu L, Altman A, Liu Y. A direct interaction between the adaptor protein Cbl-b and the kinase zap-70 induces a positive signal in T cells. Curr Biol. 1999;9:203-6 pubmed
    ..Unlike the proposed role of Cbl as a negative regulator, our results suggest that the Cbl homologue Cbl-b has a positive role in T-cell signaling, most likely via a direct interaction with the upstream kinase Zap-70. ..
  39. Thaisetthawatkul P, Weinstock A, Kerr S, Cohen M. Muromonab-CD3-induced neurotoxicity: report of two siblings, one of whom had subsequent cyclosporin-induced neurotoxicity. J Child Neurol. 2001;16:825-31 pubmed
  40. Boilard E, Surette M. Anti-CD3 and concanavalin A-induced human T cell proliferation is associated with an increased rate of arachidonate-phospholipid remodeling. Lack of involvement of group IV and group VI phospholipase A2 in remodeling and increased susceptibility of p. J Biol Chem. 2001;276:17568-75 pubmed
    ..Altogether these results indicate that increased arachidonate-phospholipid remodeling is associated with T cell proliferation and that CoA-independent transacylase may be a novel therapeutic target for proliferative disorders. ..
  41. Whiting J, Fecteau A, Martin J, Bejarano P, Hanto D. Use of low-dose OKT3 as induction therapy in liver transplantation. Transplantation. 1998;65:577-80 pubmed
    ..Low-dose OKT3 induction appears to be a safe and useful method of postoperative immunosuppression after liver transplantation. Its ultimate clinical, immunologic, and economic efficacy awaits determination by randomized trial. ..
  42. Opelz G, Naujokat C, Daniel V, Terness P, Dohler B. Disassociation between risk of graft loss and risk of non-Hodgkin lymphoma with induction agents in renal transplant recipients. Transplantation. 2006;81:1227-33 pubmed
    ..IL-2RA agents seem to offer the best risk-to-benefit ratio for this patient population overall in terms of graft survival and lymphoma. ..
  43. Smith R, Brousaides N, Grazette L, Saidman S, Semigran M, Disalvo T, et al. C4d deposition in cardiac allografts correlates with alloantibody. J Heart Lung Transplant. 2005;24:1202-10 pubmed
  44. Moffatt S, Demers P, Robbins R, Doyle R, Wienacker A, Henig N, et al. Lung transplantation: a decade of experience. J Heart Lung Transplant. 2005;24:145-51 pubmed
    ..Lung transplantation, using RATG induction therapy, remains an important modality for end-stage pulmonary disease. ..
  45. Zhang S, Li W, Zhang H, Wang Q. Antitumor reactivity of splenocytes primed in vivo with dendritic-cell-based vaccine and secondarily activated with a cocktail of cytokines in vitro. Exp Oncol. 2004;26:243-5 pubmed
    ..The result here indicates that tumor lysate pulsed DC can be used as a strategy to generate effector T cells which can be further activated with a cocktail of cytokines for adoptive immunotherapy. ..
  46. Stachel D, Fütterer A, Haas R, Schmid I. Enhanced lymphocyte proliferation responses in pediatric patients early after myelosuppressive chemotherapy. Pediatr Blood Cancer. 2004;43:644-50 pubmed
    ..Early after ChTh, a period of immunoaugmentation seems to exist. Whether this observation can be used clinically to increase cure rates remains to be elucidated. ..
  47. Lloveras J. Use of cyclosporine in renal transplantation. Transplant Proc. 2004;36:107S-113S pubmed
    ..Cyclosporine's future place is yet to be established in the new era of immunosuppression. ..
  48. Hrekova S, Vodianyk M, Chernyshov V. [Effect of progesterone and 17beta-estradiol on proinflammatory cytokine costimulatory proliferative activity]. Fiziol Zh. 2002;48:63-9 pubmed
    ..Our results suggest possible roles female steroid hormones as regulators on activity of proinflammatory cytokines and their functions in lymphocyte proliferation. ..
  49. Ivan E, Colovai A. Human Fc receptors: critical targets in the treatment of autoimmune diseases and transplant rejections. Hum Immunol. 2006;67:479-91 pubmed
    ..Pathologic conditions in which immunoglobulin-FcR interactions play a major role, as well as the outcome of treatment with intravenous immunoglobulin and monoclonal antibodies, may be influenced by targeting FcR. ..
  50. Lee Z, Lee S, Kwack K, Yeo W, Lee T, Bae S, et al. Caspase-mediated cleavage of TRAF3 in FasL-stimulated Jurkat-T cells. J Leukoc Biol. 2001;69:490-6 pubmed
    ..These findings suggest that TRAF3 may be regulated by caspases during apoptosis of T cells. ..
  51. Sabat R, Hoflich C, Docke W, Oppert M, Kern F, Windrich B, et al. Massive elevation of procalcitonin plasma levels in the absence of infection in kidney transplant patients treated with pan-T-cell antibodies. Intensive Care Med. 2001;27:987-91 pubmed
    ..PCT monitoring for evaluating infectious complications in kidney transplant patients must be very careful during pan-T-cell antibody therapy. ..
  52. Akioka Y, Hattori M, Ito K. [Muromonab CD3]. Nihon Rinsho. 2005;63 Suppl 5:747-50 pubmed
  53. Birkeland S, Hamilton Dutoit S. Is posttransplant lymphoproliferative disorder (PTLD) caused by any specific immunosuppressive drug or by the transplantation per se?. Transplantation. 2003;76:984-8 pubmed
    ..An important minority of cases are EBV negative. ..