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The role of OKT3 in clinical transplantation

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Abstract

OKT3 is a murine monoclonal anti-T cell antibody that is directed to CD3, a five-chain molecular complex found in association with the T cell receptor for antigen. OKT3 was the first monoclonal antibody to be used in organ transplantation and during the past 10 years there has been extensive experience of its use both for preventing and treating rejection in organ transplantation. OKT3 blocks T cell function by modulating CD3 and the T cell receptor from the T cell surface. A reaction to OKT3 results from cytokines released when OKT# first reacts with T cells. This reaction is generally mild but can be severe. First rejections following kidney transplantation are reversed in approximately 95% of cases. Steroid-resistant rejections are also susceptible to OKT3 but in only approximately 75% of cases. When used for prophylaxis, OKT3 completely blocks rejection in 95% of patients and significantly delays the onset of rejection in those who do reject. Antibodies to OKT3 are produced in approximately 75% of patients receiving it. However, seldom are the antibodies to OKT3 present in high titer and only in those cases is successful re-use of OKT3 prevented. As is the case with all potent immunosuppressive drugs, the use of OKT3 is associated with increased viral, specifically cytomegalovirus, infections. However, it appears that reduction of concomitant immunosuppression decreases the incidence of severe infections. Unquestionably, OKT3 has been a useful addition to the immunosuppression used for organ transplantation. In addition, its use has stimulated research on other monoclonal antibodies for use in organ transplantation.

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References

  1. Kohler G, Milstein C (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256:495–497

    Google Scholar 

  2. Kirkman RL, Araujo JL, Busch GJ (1983) Transplantation 36:620–626

    Google Scholar 

  3. Takahashi H, Okazaki H, Terasaki PI (1983) Reversal of transplant rejection by monoclonal antiblast antibody. Lancet II:1155–1158

    Google Scholar 

  4. Raftery MJ, Lang CJ, Ivory K (1985) Use of RFT2 (CD7) monoclonal antibody as prophylaxis against renal allograft rejection. Transplant Proc 17:2737–2739

    Google Scholar 

  5. Oei J, Cicciarelli J, Terasaki PI (1985) Treatment of kidney graft rejection with CHALI and CBLI monoclonal antibodies. Transplant Proc 17:2740–2743

    Google Scholar 

  6. Soulillou JP, Peyronnet P, LeMauff B (1987) Prevention of rejection of kidney transplants by monoclonal antibody directed against interleukin 2. Lancet I:1339–1342

    Google Scholar 

  7. d'Apice AJ, Thurlow PJ, Ihle BU (1987) Treatment of acute renal allograft rejection with a monoclonal antibody to a T cell antigen (HuLy-m2). Aust N Z J Med 17:210–215

    Google Scholar 

  8. Tax WJM, Heijden JMW van de, Willems JW (1987) Immunosuppression with monoclonal anti-T3 antibody (WT32) in renal transplantation. Transplant Proc 19:1905–1907

    Google Scholar 

  9. Friend PJ, Tighe H, Waldmann H (1988) Monoclonal antibodies that recognize activated human lymphocytes — experimental and clinical studies. Transplant Proc 20:265–266

    Google Scholar 

  10. Waid TH, Lucas BA, Amlot P (1988) Treatment of renal allograft rejection with T10B9 a new anti-T cell monoclonal antibody (abstract). Proceedings of the American Society for Transplant Physiology

  11. Starzl TE, Marchioro TL, Porter KA (1967) The use of heterologous antilymphoid agents in canine renal and liver homotransplantation and in human renal homotransplantation. Surg Gynecol Obsetet 124:301

    Google Scholar 

  12. Shiel AGR, Kelly GE, Storey BG (1971) Controlled clinical trial of antilymphocyte globulin in patients with renal allograft from cadaver donors. Lancet I:359–362

    Google Scholar 

  13. Shield CF, Cosimi AB, Tolkoff-Rubin N (1979) Use of antithymocyte globulin for reversal of acute allograft rejection. Transplantation 28:461–464

    Google Scholar 

  14. Hardy MA, Nowygrod R, Elberg A (1980) Use of ATG in treatment of steroid-resistant rejection. Transplantation 29:162–164

    Google Scholar 

  15. Kreis H, Mansouri R, Descamps JM (1981) Antithymocyte globulin in cadaver kidney transplantation: a randomized trial based on T cell monitoring. Kidney Inter 19:438–444

    Google Scholar 

  16. Novick AC, Braun WE, Steinmuller D (1983) A controlled prospective randomized double blind study of antilymphoblast globulin in cadaver renal transplantation. Transplantation 35: 175–179

    Google Scholar 

  17. Nelson PW, Cosimi AB, Delmonico FL (1983) Antithymocyte globulin as the primary treatment for renal allograft rejection. Transplantation 36:587–588

    Google Scholar 

  18. Fassbinder W, Scheuermann EH, Hanke P (1985) Improved graft prognosis by treatment of steroid-resistant rejection with rabbit antithymocyte globulin and/or plasmapheresis. Transplant Proc 17: 2769–2772

    Google Scholar 

  19. Delmonico FL, Auchincloss H Jr, Rubin RH (1987) The selective use of antilymphocyte serum for cyclosporine treated patients with renal allograft dysfunction. Ann Surg 206:649–654

    Google Scholar 

  20. Cosimi AB, Burton RC, Colvin RB (1981) Treatment of acute renal allograft rejection with OKT3 monoclonal antibody. Transplantation 32:535–539

    Google Scholar 

  21. Thistlethwaite JR Jr, Cosimi AB, Delmonico FL (1984) Evolving use of OKT3 monoclonal antibody for treatment of renal allograft rejection. Transplantation 38:695–701

    Google Scholar 

  22. Norman DJ, Shield DF III, Barry JM (1987) Therapeutic use of OKT3 monoclonal antibody for acute renal allograft rejection. Nephron 46:41–47

    Google Scholar 

  23. Leone MR, Alexander SR, Barry JM (1987) OKT3 monoclonal antibody in pediatric kidney transplant recipients with recurrent and resistant allograft rejection. J Pediatr 111:45–50

    Google Scholar 

  24. Fung JJ, Markus BH, Gordon RD (1987) Impact of Orthoclone OKT3 on liver transplantation. Transplant Proc 19:37–44

    Google Scholar 

  25. Kahana L, Baxter J (1987) OKT3 rescue in refractory renal rejection. Nephron 46:34–40

    Google Scholar 

  26. Ponticelli C (1987) Treatment of severe rejection of kidney transplants with Orthoclone OKT3. Clin Transplant 1:99–103

    Google Scholar 

  27. Costanzo-Nordin MR, Silver MA, O'Connell JB (1987) Successful reversal of acute cardiac allograft rejection with OKT3 monoclonal antibody. Circulation 76:71–80

    Google Scholar 

  28. Bristow MR (1988) Use of OKT3 monoclonal antibody in heart transplantation: review of the initial experience. J Heart Transplant 7:1–11

    Google Scholar 

  29. Deierhoi MH, Barber WH, Curtis JJ (1988) A comparison of OKT3 monoclonal antibody and corticosteroids in the treatment of acute renal allograft rejection. Am J Kidney Dis 11:86–89

    Google Scholar 

  30. Kung P, Goldstein G, Reinherz EL (1979) Monoclonal antibodies defining distinctive human T cell surface antigens. Science 206: 347–349

    Google Scholar 

  31. Chang TW, Kung PC, Gingras SP (1981) Does OKT3 monoclonal antibody react with an antigen-recognition structure on human T cells? Proc Natl Acad Sci USA 78:1805–1808

    Google Scholar 

  32. Reinherz EL, Meuer S, Fitzgerald KA (1982) Antigen recognition by human T lymphocytes is linked to surface expression of the T3 molecular complex. Cell 30:735–743

    Google Scholar 

  33. Oettgen HC, Terhorst C, Cantley LC (1985) Stimulation of the T3-T cell receptor complex induces amembrane-potential-sensitive calcium influx. Cell 40:583–590

    Google Scholar 

  34. Rosoff PM, Cantley LC (1985) Stimulation of the T3-T cell receptor-associated Ca2+-influx enhances the activity of the Na+/H+ exchanger in a leukemic human T cell line. J Biol Chem 260:14053–14059

    Google Scholar 

  35. Van Wauwe JP, Goossens JG (1983) The mitogenic activity of OKT3 and anti-Leu 4 monoclonal antibodies: a comparative study. Cell Immunol 77:23–29

    Google Scholar 

  36. Landegren U, Andersson J, Wigzell H (1984) Mechanism of T lymphocyte activation by OKT3 antibodies: a general model for T cell induction. Eur J Immunol 14:325–328

    Google Scholar 

  37. Van Wauwe JP, Goossens JG, Beverley PC (1984) Human T lymphocyte activation by monoclonal antibodies; OKT3, but not UCHT1, triggers mitogenesis via an interleukin 2-dependent mechanism. J Immunol 133:129–132

    Google Scholar 

  38. Schwab R, Crow MK, Russon C (1985) Requi rements for T cell activation by OKT3 monoclonal antibody: role of modulation of T3 molecules and interleukin 1. J Immunol 135:1714–1718

    Google Scholar 

  39. Palacios R (1985) Mechanisms by which accessory cells contribute in growth of resting T lymphocytes initiated by OKT3 antibody. Eur J Immunol 15:645–651

    Google Scholar 

  40. Geppert TD, Lipsky PE (1986) Accessory cell-T cell interactions involved in anti-CD3-induced T4 and T8 cell proliferation: analysis with monoclonal antibodies. J Immunol 137:3065–3073

    Google Scholar 

  41. Looncy RJ, Abraham GN (1984) The Fc portion of intact IgG blocks stimulation of human PBMC by anti-T3. J Immunol 133: 154–156

    Google Scholar 

  42. Ceuppens J, Bloemmen FJ, Van Wauwe JP (1985) T cell unresponsiveness to the mitogenic activity of OKT3 antibody results from a deficiency of monocyte Fc gamma receptors for murine IgG2a and inability to cross-link the T3-Ti complex. J Immunol 135:3882–3886

    Google Scholar 

  43. Ceuppens JL, Meurs L, Van Wauwe JP (1985) Failure of OKT3 monoclonal antibody to induce lymphocyte mitogenesis: a familial defect in monocyte helper function. J Immunol 134:1498–1502

    Google Scholar 

  44. Papadogiannakis N, Johnsen SA, Olding LB (1986) Monocyte-regulated hyporesponsiveness of human cord blood lymphocytes to OKT3-monoclonal-antibody-induced mitogenesis. Scand J Immunol 23:91–99

    Google Scholar 

  45. Smith KG, Austyn JM, Hariri G (1986) T cell activation by anti-T3 antibodies: comparison of IgG1 and IgG2b switch variants and direct evidence for accessory function of macrophage Fc receptors. Eur J Immunol 16:478–486

    Google Scholar 

  46. Chang TW, Gingras SP (1981) OKT3 monoclonal antibody inhibits cytotoxic T lymphocyte mediated cell lysis. Int J Immunopharmacol 3:183–186

    Google Scholar 

  47. Kammer GM, Kurrasch R, Scillian JJ (1984) Capping of the surface OKT3 binding molecule prevents the T-cell proliferative response to antigens: evidence that this molecule conveys the activation signal. Cell Immunol 87:284–294

    Google Scholar 

  48. Brenner MB, Trowbridge IS, Strominger JL (1985) Cross-linking of human T cell receptor proteins: association between the T cell idiotype beta subunit and the T3 glycoprotein heavy subunit. Cell 40:183–190

    Google Scholar 

  49. Wang CY, Bushkin Y, Pica R (1986) Stimulation and expansion of a human T-cell subpopulation by a monoclonal antibody to T-cell receptor molecule. Hybridoma 5:179–190

    Google Scholar 

  50. Goldstein G, Norman DJ, Henell KR (1987) Pharmacokinetic study of Orthoclone OKT3 serum levels during treatment of acute renal allograft rejection. Transplantation 44:587–589

    Google Scholar 

  51. Waldman TA, Strober W, Blaese RM (1970) Immunoglobulins. National Academy of Sciences, Washington, DC

    Google Scholar 

  52. Chatenoud L, Baudrihaye MF, Kreis H (1982) Human in vivo antigenic modulation induced by the anti-T cell OKT3 monoclonal antibody. Eur J Immunol 12:979–982

    Google Scholar 

  53. Delmonico FL (1985) T cell subset alterations in OKT3-treated patients. Transplant Proc 17:628–629

    Google Scholar 

  54. Shield CF, Norman DJ (1988) Immunologic monitoring during and after OKT3 therapy. Am J Kidney Dis 11:120–124

    Google Scholar 

  55. Rinnooy Kan EA, Wright SD, Welte K (1986) Fc receptors on monocytes cause OKT3-treated lymphocytes to internalize T3 and to secrete IL-2. Cell Immunol 98:181–187

    Google Scholar 

  56. Cosimi AB (1987) OKT3: first-dose safety and success. Nephron 46:12–18

    Google Scholar 

  57. Rowe PA, Rocker GM, Morgan AG (1987) OKT3 and pulmonary capillary permeability. Br Med J 295:1099–1100

    Google Scholar 

  58. Hosenpud JD Norman DJ, Pantley GA (1989) OKT3 induced hypotension in cardiac allograft recipients, treated for resistant rejection. J Heart Transplant 8:159–166

    Google Scholar 

  59. Emmons C, Smith J, Flanigan M (1986) Cerebrospinal fluid inflammation during OKT3 therapy (letter). Lancet II:510–511

    Google Scholar 

  60. Thomas DM, Nicholls AJ, Feest TG (1987) OKT3 and cerebral oedema. Br Med J 295:1486

    Google Scholar 

  61. Martin MA, Massanari RM, Nghiem DD (1988) Nosocomial aseptic meningitis associated with administration of OKT3. JAMA 259: 2002–2005

    Google Scholar 

  62. Chang TW, Testa D, Kung PC (1982) Cellular origin and interactions involved in gamma-interferon production induced by OKT3 monoclonal antibody. J Immunol 128:585–589

    Google Scholar 

  63. Abramowicz D, Schandene L, Goldman M (1989) Release of tumor necrosis factor, interleukin-2, and gamma-interferon in serum after injection of OKT3 monoclonal antibody in kidney transplant recipients. Transplantation 47:606–608

    Google Scholar 

  64. Belldegrun A, Webb DE, Austin HA III (1987) Effects of interleukin-2 on renal function in patients receiving immunotherapy for advanced cancer. Ann Intern Med 106:817–822

    Google Scholar 

  65. Dierckx RA, Michotte A, Schmedding E (1985) Unilateral seizures in a patient with hairy cell leukemia treated with interferon. Clin Neurol Neurosurg 87:209–212

    Google Scholar 

  66. Sriskandan K, Garner P, Watkinson J (1987) A toxicity study of recombinant interferon-gamma given by intravenous infusion to patients with advanced cancer. Cancer Chemother Pharmacol 18: 63–68

    Google Scholar 

  67. Denicoff KD, Rubinow DR, Papa MZ (1987) The neuropsychiatric effects of treatment with interleukin-2 and lymphokine-activated killer cells. Ann Intern Med 107:293–300

    Google Scholar 

  68. Talmadge JE (1987) Toxicity of tumor necrosis factor, is synergistic with gamma-interferon, and can be reduced with cyclooxygenase inhibitors. Am J Pathol 128:410–425

    Google Scholar 

  69. Thompson JA, Lee DJ, Cox WW (1987) Recombinant interleukin 2 toxicity, pharmacokinetics, and immunomodulatory effects in a phase I trail. Cancer Res 47:4202–4207

    Google Scholar 

  70. Vetto JT, Papa MZ, Lotze MT (1987) Reduction of toxicity of interleukin-2 and lymphokine-activated killer cells in humans by the administration of corticosteroids. J Clin Oncol 5:496–503

    Google Scholar 

  71. Bertram JH, Gill PS, Levine AM (1986) Monoclonal antibody T101 in T cell malignancies: a clinical, pharmacokinetic, and immunologic correlation. Blood 68:752–761

    Google Scholar 

  72. Goldstein G, Fuccello AG, Norman DJ (1986) OKT3 monoclonal antibody plasma levels during therapy and the subsequent development of host antibodies to OKT3. Transplantation. 42:507–511

    Google Scholar 

  73. Shield CF, Norman DJ, Marlett P (1987) Comparison of antimouse and antihorse antibody production during the treatment of allograft rejection with OKT3 or antithymocyte globulin. Nephron 46: 48–51

    Google Scholar 

  74. Baudrihaye MF, Chatenoud L, Kreis H (1984) Unusually restricted anti-isotype human immune response to OKT3 monoclonal antibody. Eur J Immunol 14:686–691

    Google Scholar 

  75. Chatenoud L, Baudrihaye MF, Chkoff N (1986) Restriction of the human in vivo immune response against the mouse monoclonal antibody OKT3. J Immunol 137:830–838

    Google Scholar 

  76. Jaffers GJ, Fuller TC, Cosimi AB (1986) Monoclonal antibody therapy: anti-idiotypic and non-anti-idiotypic antibodies to OKT3 arising despite intense immunosuppression. Transplantation 41: 572–578

    Google Scholar 

  77. Chatenoud L, Jonker M, Villemain F (1986) The human immune response to the OKT3 monoclonal antibody is oligoclonal. Science 232:1406–1408

    Google Scholar 

  78. Norman DJ, Shield CF, Henell K (1988) Effectiveness of a second course of OKT3 for treatment of renal allograft rejection. Transplantation 46:523–529

    Google Scholar 

  79. Jonker M, DenBrok JHAM (1987) Idiotype switching of CD4-specific monoclonal antibodies can prolong the therapeutic effectiveness in spite of host anti-mouse IgG antibodies. Eur J Immunol 17: 1547–1553

    Google Scholar 

  80. Shield CF, Hughes JD, Marlett P (1989) The human anti-mouse response to OKT3: crossreactive pattern analysis using a large group of anti-CD3 and isotypic monoclonal antibodies. Transplant Proc 21:981–984

    Google Scholar 

  81. Vigeral P, Chkoff N, Chatenoud L (1986) Prophylactic use of OKT3 monoclonal antibody in cadaver kidney recipients: utilization of OKT3 as the sole immunosuppressive agent. Transplantation 41:730–733

    Google Scholar 

  82. Thistlethwaite JR, Stuart JK, Mayes JT (1988) Use of a brief steroid trial before initiating OKT3 therapy for renal allograft rejection. Am J Kidney Dis 11:94–98

    Google Scholar 

  83. Waldman H (1988) Monoclonal antibodies for organ transplantation: prospects for the future. Am J Kidney Dis 11:154–158

    Google Scholar 

  84. Ortho Multicenter Transplant Study Group (1985) A randomized clinical trial of OKT3 monoclonal antibody for acute rejection of cadaveric renal transplants. N Eng J Med 313:337–342

    Google Scholar 

  85. Cosimi AB, Wortis HH, Delmonico FL (1976) Randomized clinical trial of ATG in cadaver renal allograft recipients: importance of T cell monitoring. Surgery 80:155–163

    Google Scholar 

  86. Goldstein G, Norman DJ, Shield CF III (1986) OKT3 monoclonal antibody reversal of acute renal allograft rejection unresponsive to conventional immunosuppressive treatmebts. Prog Clin Biol Res 224:239–249

    Google Scholar 

  87. Thistlethwaite JR Jr, Gaber AO, Haag BW (1987) OKT3 treatment of steroid-resistant renal allograft rejection. Transplantation 43: 176–185

    Google Scholar 

  88. Norman DJ, Barry JM, Bennett WM (1988) The use of OKT3 in cadaveric renal transplantation for rejection that is unresponsive to conventional anti-rejection therapy. Am J Kidney Dis 11:90–93

    Google Scholar 

  89. Delaney VB, Campbell WG Jr, Nasr SA (1988) Efficacy of OKT3 monoclonal antibody therapy in steroid-resistant, predominantly vascular acute rejection. Transplantation 45:743–748

    Google Scholar 

  90. Rubin MF, Nghiem DD, Stachura I (1988) Late steroid-resistant rejection response to OKT3. Transplantation 45:818–819

    Google Scholar 

  91. Jeaneet M, Pinn VW, Flax MH (1970) Humoral antibodies in renal allo-transplantation in man. N Engl J Med 282:111–117

    Google Scholar 

  92. Hirsch RL, Layton PC, Barnes LA (1987) Orthoclone OKT3 treatment of acute renal allograft rejection in patients receiving maintenance cyclosporine therapy. Transplant Proc 19:32–36

    Google Scholar 

  93. Thistlethwaite JR, Haag BW, Gaber AO (1987) The use of OKT3 to treat steroid-resistant renal allograft rejection in patients receiving cyclosporine. Transplant Proc 19:1901–1904

    Google Scholar 

  94. Vigeral P (1985) Prophylactic treatment of kidney transplant recipients with a monoclonal anti-T cell antibody (OKT3-PAN). Monoclonal antibody: diagnostic and therapeutic use in tumor and transplantation PSG, Littleton, pp 79–83

  95. Debure A, Chkoff N, Chatenoud L (1988) One-month prophylactic use of OKT3 in cadaver kidney transplant recipients. Transplantation 45:546–553

    Google Scholar 

  96. Klein JB (1988) Sustained periods without rejection after treatment of cardiac allograft recipients with OKT3. Transplant Proc 20: 260–262

    Google Scholar 

  97. Ackermann JR (1988) Prophylactic use of OKT3 in renal transplantion: part of a prospective randomized multicenter trial. Transplant Proc. 20:242–244

    Google Scholar 

  98. Norman DJ, Shield CF 3rd, Barry J (1988) Early use of OKT3 monoclonal antibody in renal transplantation to prevent rejection. Am J Kidney Dis 11:107–110

    Google Scholar 

  99. Kreis H (1985) Prophylactic treatment of allograft recipients with a monoclonal anti-T3+ cell antibody. Transplant Proc 17:1315–1319

    Google Scholar 

  100. Bristow MR, Gilbert, EM, O'Connell JB (1988) OKT3 monoclonal antibody in heart transplantation. Am J Kidney Dis 11:135–140

    Google Scholar 

  101. Mayes JT, Thistlethwaite JR, Jr, Stuart JK (1988) Re-exposure to OKT3 in renal allograft recipients. Transplantation 45:349–353

    Google Scholar 

  102. Singh N (1988) Impact of OKT3 therapy on cytomegalovirus and herpes simplex virus infections after liver transplantation. Transplant Proc 20:661–662

    Google Scholar 

  103. Oh CS, Stratta RJ, Fox BC (1988) Increased infections associated with the use of OKT3 for treatment of steroid-resistant rejection in renal transplantation. Transplantation 45:68–73

    Google Scholar 

  104. Chou S, Norman DJ (1985) Effect of OKT3 antibody therapy on cytomegalovirus reactivation in renal transplant recipients. Transplant Proc 17:2755–2756

    Google Scholar 

  105. Chou S, Kim DY, Norman DJ (1987) Transmission of cytomegalovirus by pretransplant leukocyte transfusions in renal transplant candidates. J Infect Dis 155:565–567

    Google Scholar 

  106. Leone MR, Barry JM (1990) Monoclonal antibody OKT3 therapy in pediatric kidney transplant recipients. J Pediatr 116:S86-S91

    Google Scholar 

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Norman, D.J., Leone, M.R. The role of OKT3 in clinical transplantation. Pediatr Nephrol 5, 130–136 (1991). https://doi.org/10.1007/BF00852870

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