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The Experimental and Clinical Use in Transplantation of Monoclonal Antibodies to CD4 and Other Adhesion Molecules

  • John Powelson
  • A. Benedict Cosimi
Part of the Medical Intelligence Unit book series (MIU.LANDES)

Abstract

Monoclonal antibody (MoAb) technology has made possible the production of designer proteins specifically reactive with almost any conceivable biological molecule. The CD3 antigen was selected as one of the first targets for MoAb-based immunosuppression because it is present as part of the T-cell receptor (TCR) on all mature T cells. Disabling these cells, the pivotal actors in the alloresponse, was predicted to provide an effective approach to interrupting the rejection response in a more selective manner than that previously provided by polyclonal antilymphocyte preparations. The expected immunosuppressive effectiveness of anti-CD3 MoAb therapy has now been extensively confirmed in numerous clinical trials of OKT3.1-6 Monoclonal antibodies reactive with other epitopes on the TCR have also been found to be capable of reversing allograft rejection.7,8 However, suppressing all T cells indiscriminately increases the risk of infections and malignancies, while not necessarily being essential for effective immunosuppression. Suppressing selected T-cell subsets might provide comparably effective immunosuppression with less potential morbidity than these pan-T-cell reagents. Accordingly, MoAbs have been developed against targets such as the CD4 antigen, expressed on the T-cell subset involved in sensitization to the allograft (CD4+ T cells); and the adhesion molecules, essential elements in the “second signal” required for T-cell activation.

Keywords

Renal Allograft Cardiac Allograft Allograft Survival Anti Thymocyte Globulin Renal Allograft Recipient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Cosimi AB, Burton RC, Colvin RB et al. Treatment of acute renal allograft rejection with OKT3 monoclonal antibody. Transplantation 1981; 32: 535–539.PubMedCrossRefGoogle Scholar
  2. 2.
    Cosimi AB, Cho SI, Delmonico FL et al. A randomized clinical trial comparing OKT3 and steroids for treatment of hepatic allograft rejection. Transplant Proc 1987; 19: 2431–2433.PubMedGoogle Scholar
  3. 3.
    Farges C, Samuel D, Bismuth H. Orthoclone OKT3 in liver transplantation. Transplantation Science 1992; 2:16–21.Google Scholar
  4. 4.
    Ortho Multicenter Transplant Study Group. A randomized clinical trial of OKT3 monoclonal antibody for acute rejection of cadaveric renal transplants. N Engl J Med 1985; 313: 337–342.CrossRefGoogle Scholar
  5. 5.
    Ponticelli C, Rivolta E, Tarantino A et al. Treatment of severe rejection of kidney transplant with Orthoclone OKT3. Clin Transplantation 1987; 1: 99–103.Google Scholar
  6. 6.
    Robbins RC, Oyer PE, Stinson EB et al. The use of monoclonal antibodies after heart transplantation. Transplant Sci 1992; 2: 22–27.Google Scholar
  7. 7.
    Waid TH, Lucas BA, Thompson JS et al. Treatment of acute cellular rejection with T10B9.1A-31 or OKT3 in renal allograft recipients. Transplantation 1992; 53: 80–86.PubMedCrossRefGoogle Scholar
  8. 8.
    Frenken LA, Hoitsma AJ, Tax WJ et al. Prophylactic use of anti-CD3 monoclonal antibody WT32 in kidney transplantation. Transplant Proc 1991; 23: 1072–1073.PubMedGoogle Scholar
  9. 9.
    Sablinski T, Hancock WW, Tilney NL et al. CD4 monoclonal antibodies in organ transplantation—a review of progress. Transplantation 1991; 52: 579–589.PubMedCrossRefGoogle Scholar
  10. 10.
    Auchincloss HJ, Sachs DH. Transplantation and graft rejection. In: Paul WE, ed. Fundamental Immunology. 3rd ed. New York: Raven Press, 1993: 1099–1141.Google Scholar
  11. 11.
    Doyle C. Interaction between CD4 and class II MHC molecules mediates cell adhesion. Nature 1987; 330: 256–259.PubMedCrossRefGoogle Scholar
  12. 12.
    Springer TA. Adhesion receptors of the immune system. Nature 1990; 346: 425–34.PubMedCrossRefGoogle Scholar
  13. 13.
    Weiss A. T lymphocyte activation. In: Paul WE, ed. Fundamental Immunology. 3rd ed. New York: Raven Press, 1993: 467–504.Google Scholar
  14. 14.
    Swain ST. T cell subsets and the recognition of MHC class. Immunol Rev 1983; 74: 129–142.PubMedCrossRefGoogle Scholar
  15. 15.
    Sprent J, Webb SR. Function and specificity of T cell subsets in the mouse. Adv Immunol 1987; 41: 39–133.PubMedCrossRefGoogle Scholar
  16. 16.
    Bishop DK, Shelby J, Eichwald EJ. Mobilization of T lymphocytes following cardiac transplantation. Evidence that CD4-positive cells are required for cytotoxic T lymphocyte activation, inflammatory endothelial development, graft infiltration, and acute allograft rejection. Transplantation 1992; 53: 849–57.PubMedCrossRefGoogle Scholar
  17. 17.
    Rosenberg AS, Munitz TI, Maniero TG et al. Cellular basis of skin allograft rejection across a class I major histocompatibility barrier in mice depleted of CD8+ T cells in vivo. J Exp Med 1991; 173: 1463–1471.PubMedCrossRefGoogle Scholar
  18. 18.
    Bishop DK, Chan S, Li W et al. CD4-positive helper T lymphocytes mediate mouse cardiac allograft rejection independent of donor alloantigen specific cytotoxic T lymphocytes. Transplantation 1993; 56: 892–897.PubMedCrossRefGoogle Scholar
  19. 19.
    Sayegh MH, Sablinski T, Tanaka K et al. Effects of BWH-4 anti-CD4 monoclonal antibody on rat vascularized cardiac allografts before and after engraftment. Transplantation 1991; 51: 296–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Sablinski T, Sayegh MH, Kut JP et al. The importance of targeting the CD4+ T cell subset at the time of antigenic challenge for induction of prolonged vascularized allograft survival. Transplantation 1992; 53: 219–21.PubMedGoogle Scholar
  21. 21.
    Cosimi AB, Delmonico FL, Wright JK et al. Prolonged survival of nonhuman primate renal allograft recipients treated only with anti-CD4 monoclonal antibody. Surgery 1990; 108: 406–13.PubMedGoogle Scholar
  22. 22.
    Greenwood J, Clark M, Waldmann H. Structural motifs involved in human IgG antibody effector functions. Eur J Immunol 1993; 23: 1098–104.PubMedCrossRefGoogle Scholar
  23. 23.
    Hancock WW, Sayegh MH, Sablinski T et al. Blocking of mononuclear cell accumulation, cytokine production, and endothelial activation within rat cardiac allografts by CD4 monoclonal antibody therapy. Transplantation 1992; 53: 1276–80.PubMedCrossRefGoogle Scholar
  24. 24.
    Shizuru JA, Seydel KB, Flavin TF et al. Induction of donor-specific unresponsiveness to cardiac allografts in rats by pretransplant anti-CD4 monoclonal antibody therapy. Transplantation 1990; 50: 366–373.PubMedCrossRefGoogle Scholar
  25. 25.
    Pearson TC, Bushell AR, Darby CR et al. Lymphocyte changes associated with prolongation of cardiac allograft survival in adult mice using anti-CD4 monoclonal antibody. Clin Exp Immunol 1993; 92: 211–7.PubMedCrossRefGoogle Scholar
  26. 26.
    Darby CR, Bushell A, Morris PJ et al. Nondepleting anti-CD4 antibodies in transplantation. Evidence that modulation is far less effective than prolonged CD4 blockade. Transplantation 1994; 57: 1419–26.PubMedGoogle Scholar
  27. 27.
    Powelson JA, Knowles RW, Delmonico FL et al. CDR-grafted OKT4A monoclonal antibody in cynomolgus renal allograft recipients. Transplantation 1994; 57: 788–93.PubMedCrossRefGoogle Scholar
  28. 28.
    Horneff G, Emmrich F, Reiter C et al. Persistent depletion of CD4+ T cells and inversion of the CD4/CD8 T cell ratio induced by anti-CD4 therapy. J Rheumatol 1992; 19: 1845–50.PubMedGoogle Scholar
  29. 29.
    Sprent J. T lymphocytes and the thymus. In: Paul WE, ed. Fundamental Immunology. 3rd ed. New York: Raven Press, 1993: 75–109.Google Scholar
  30. 30.
    Kisielow P, Bluthmann H, Staerz UD et al. Tolerance in T-cell-receptor transgenic mice involves deletion of nonmature CD4+8+ thymocytes. Nature 1988; 333: 742–6.PubMedCrossRefGoogle Scholar
  31. 31.
    O’Toole CM, Maher P, Spiegelhalter DJ et al. ‘Rejection or infection’ predictive value of T-cell subject ratio, before and after heart transplantation. J Heart Transplant 1985; 4: 518–24.PubMedGoogle Scholar
  32. 32.
    Shen SY, Weir MR, Kosenko A et al. Reevaluation of T cell subset monitoring in cyclosporine-treated renal allograft recipients. Transplantation 1985; 40: 620–3.PubMedCrossRefGoogle Scholar
  33. 33.
    Darby CR, Morris PJ, Wood KJ. Evidence that long-term cardiac allograft survival induced by anti-CD4 monoclonal antibody does not require depletion of CD4+ T cells. Transplantation 1992; 54: 483–90.PubMedCrossRefGoogle Scholar
  34. 34.
    Burkhardt K, Charlton B, Mandel TE. An increase in the survival of murine H-2-mismatched cultured fetal pancreas allografts using depleting or nondepleting anti-CD4 monoclonal antibodies, and a further increase with the addition of cyclosporine. Transplantation 1989; 47: 771–5.PubMedCrossRefGoogle Scholar
  35. 35.
    Lehmann M, Sternkopf F, Metz F et al. Induction of long-term survival of rat skin allografts by a novel, highly efficient anti-CD4 monoclonal antibody. Transplantation 1992; 54: 959–62.PubMedCrossRefGoogle Scholar
  36. 36.
    Wee SL, Stroka DM, Preffer FI et al. The effects of OKT4A monoclonal antibody on cellular immunity of nonhuman primate renal allograft recipients. Transplantation 1992; 53: 501–7.PubMedCrossRefGoogle Scholar
  37. 37.
    Tite JP, Sloan A, Janeway CJ. The role of L3T4 in T cell activation: L3T4 may be both an la-binding protein and a receptor that transduces a negative signal. J Mol Cell Immunol 1986; 2: 179–190.PubMedGoogle Scholar
  38. 38.
    Pearson TC, Madsen JC, Larsen CP et al. Induction of transplantation tolerance in adults using donor antigen and anti-CD4 monoclonal antibody. Transplantation 1992; 54: 475–83.PubMedCrossRefGoogle Scholar
  39. 39.
    Bushell A, Morris PJ, Wood KJ. Induction of operational tolerance by random blood transfusion combined with anti-CD4 antibody therapy. A protocol with significant clinical potential. Transplantation 1994; 58: 133–9.Google Scholar
  40. 40.
    Qin SX, Wise M, Cobbold SP et al. Induction of tolerance in peripheral T cells with monoclonal antibodies. Eur J Immunol 1990; 20: 2737–2745.PubMedCrossRefGoogle Scholar
  41. 41.
    Bretscher P. The two-signal model of lymphocyte activation twenty-one years later. Immunol Today 1993; 13: 74–76.CrossRefGoogle Scholar
  42. 42.
    Pearson TC, Hamano K, Morris PJ et al. Anti-CD4 monoclonal antibody-induced allograft survival is associated with a defect in interleukin-2-dependent T-cell activation. Transplant Proc 1993; 25: 786–7.PubMedGoogle Scholar
  43. 43.
    Herbert J, Roser B. Strategies of monoclonal antibody therapy that induce permanent tolerance of organ transplants. Transplantation 1988; 46: 128S–134S.PubMedCrossRefGoogle Scholar
  44. 44.
    Alters SE, Song HK, Fathman CG. Evidence that clonal anergy is induced in thymic migrant cells after anti-CD4-mediated transplantation tolerance. Transplantation 1993; 56: 633–8.PubMedCrossRefGoogle Scholar
  45. 45.
    Heinrich G, Gram H, Kocher HP et al. Characterization of a human T cell-specific chimeric antibody (CD7) with human constant and mouse variable regions. J Immunol 1989; 143: 3589–3597.PubMedGoogle Scholar
  46. 46.
    Riechmann L, Clark M, Waldmann H et al. Reshaping human antibodies for therapy. Nature 1988; 332: 323–7.PubMedCrossRefGoogle Scholar
  47. 47.
    Boulianne GL, Hozumi N, Shulman MJ. Production of functional chimaeric mouse/human antibody. Nature 1984; 312: 643–6.PubMedCrossRefGoogle Scholar
  48. 48.
    Delmonico FL, Cosimi AB, Kawai T et al. Non-human primate responses to murine and humanized OKT 4A. Transplantation 1993; 55: 722–728.PubMedCrossRefGoogle Scholar
  49. 49.
    Meiser BM, Reiter C, Reichenspurner H et al. Chimeric monoclonal CD4 antibody—a novel immunosuppressant for clinical heart transplantation. Transplantation 1994; 58: 419–23.PubMedCrossRefGoogle Scholar
  50. 50.
    Horneff G, Burmester GR, Emmrich F et al. Treatment of rheumatoid arthritis with an anti-CD4 monoclonal antibody. Arthritis Rheum 1991; 34: 129–140.PubMedCrossRefGoogle Scholar
  51. 51.
    Reinke P, Volk HD, Miller H et al. Anti-CD4 therapy of acute rejection in long-term renal allograft recipients [letter]. Lancet 1991; 338: 702–3.PubMedCrossRefGoogle Scholar
  52. 52.
    Morel P, Vincent C, Cordier G et al. Anti-CD4 monoclonal antibody administration in renal transplanted patients. Clin Immunol Immunopathol 1990; 56: 311–22.PubMedCrossRefGoogle Scholar
  53. 53.
    Land W. Monoclonal antibodies in 1991: new potential options in clinical immunosuppressive therapy. Clin Transplantation 1991; 5: 493–500.Google Scholar
  54. 54.
    Tilney NL, Kupiec-Weglinski JW. The immunobiology of acute allograft rejection. In: Brent L, Sells RA, eds. Organ Transplantation: Current Clinical and Immunological Concepts. London: Bailliere Tindall, 1989: 19–38.Google Scholar
  55. 55.
    Grisham MB, Hernandez LA, Granger DN. Xanthine oxidase and neutrophil infiltration in intestinal ischemia. Am J Physiol 1986; 251: G567–G574.PubMedGoogle Scholar
  56. 56.
    Pober JS, Cotran RS. The role of endothelial cells in inflammation. Transplantation 1990; 50: 537–544.PubMedCrossRefGoogle Scholar
  57. 57.
    Lasky LA. Selectins: interpreters of cell-specific carbohydrate information during inflammation. Science 1992; 258: 964–969.PubMedCrossRefGoogle Scholar
  58. 58.
    Mulligan MS, Paulson JC, De Frees S et al. Protective effects of oligosaccharides in P-selectin-dependent lung injury. Nature 1993; 364: 149–51.PubMedCrossRefGoogle Scholar
  59. 59.
    Azuma H, Heemann UW, Tullius SG et al. Cytokines and adhesion molecules in chronic rejection. Clin Transplant 1994; 8: 168–80.PubMedGoogle Scholar
  60. 60.
    Gearing A, Newman W. Circulating adhesion molecules in disease. Immunol Today 1993; 14: 506–512.PubMedCrossRefGoogle Scholar
  61. 61.
    Heemann UW, Tullius SG, Azuma H et al. Adhesion molecules and transplantation. Ann Surg 1994; 219: 4–12.PubMedCrossRefGoogle Scholar
  62. 62.
    Shevach EM. Accessory molecules. In: Paul WE, ed. Fundamental Immunology. 3rd ed. New York: Raven Press, 1993: 531–575.Google Scholar
  63. 63.
    Zimmerman GA, Prescott SM, McIntyre TM. Endothelial cell interactions with granulocytes: tethering and signaling molecules. Immunol Today 1992; 13: 93–100.PubMedCrossRefGoogle Scholar
  64. 64.
    Berg EL, McEvoy LM, Berlin C et al. L-selectin-mediated lymphocyte rolling on MAdCAM-1 [see comments]. Nature 1993; 366: 695–8.PubMedCrossRefGoogle Scholar
  65. 65.
    Shimizu Y, Newman W, Tanaka Y et al. Lymphocyte interactions with endothelial cells. Immunol Today 1992; 13: 106–12.PubMedCrossRefGoogle Scholar
  66. 66.
    Kato K, Koyanagi M, Okada H et al. CD48 is a counter-receptor for mouse CD2 and is involved in T cell activation. J Exp Med 1992; 176: 1241–9.PubMedCrossRefGoogle Scholar
  67. 67.
    Van Seventer G, Shimizu Y, Horgan KJ et al. The LFA-1 ligand ICAM-1 provides an important costimulatory signal for T cell receptor-mediated activation of resting T cells. J Immunol 1990; 144: 4579–86.PubMedGoogle Scholar
  68. 68.
    Bierer BE, Sleckman BP, Ratnofsky SE et al. The biologic roles of CD2, CD4, and CD8 in T-cell activation. Annu Rev Immunol 1989; 7: 579–99.PubMedCrossRefGoogle Scholar
  69. 69.
    Isobe M, Yagita H, Okumura K et al. Specific acceptance of cardiac allograft after treatment with antibodies to ICAM-1 and LFA-1. Science 1992; 255: 1125–7.PubMedCrossRefGoogle Scholar
  70. 70.
    Qin L, Chavin KD, Lin J et al. Anti-CD2 receptor and anti-CD2 ligand (CD48) antibodies synergize to prolong allograft survival. J Exp Med 1994; 179: 341–6.PubMedCrossRefGoogle Scholar
  71. 71.
    Orosz CG, Ohye RG, Pelletier RP et al. Treatment with anti-vascular cell adhesion molecule 1 monoclonal antibody induces longterm murine cardiac allograft acceptance. Transplantation 1993; 56: 453–60.PubMedCrossRefGoogle Scholar
  72. 72.
    Cosimi AB, Conti D, Delmonico FL et al. In vivo effects of monoclonal antibody to ICAM-1 (CD54) in nonhuman primates with renal allografts. J Immunol 1990; 144: 4604–4612.PubMedGoogle Scholar
  73. 73.
    Klausner JM, Anner H, Paterson IS et al. Lower torso ischemia-induced lung injury is leukocyte dependent. Ann Surg 1988; 208: 761–7.PubMedCrossRefGoogle Scholar
  74. 74.
    Entman ML, Michael L, Rossen RD et al. Inflammation in the course of early myocardial ischemia. Faseb J 1991; 5: 2529–37.PubMedGoogle Scholar
  75. 75.
    Ma XL, Weyrich AS, Lefer DJ et al. Monoclonal antibody to L-selectin attenuates neutrophil accumulation and protects ischemic reperfused cat myocardium. Circulation 1993; 88: 649–58.PubMedCrossRefGoogle Scholar
  76. 76.
    Byrne JG, Smith WJ, Murphy MP et al. Complete prevention of myocardial stunning, contracture, low-reflow, and edema after heart transplantation by blocking neutrophil adhesion molecules during reperfusion. J Thorac Cardiovasc Surg 1992; 104: 1589–96.PubMedGoogle Scholar
  77. 77.
    Clark WM, Madden KP, Rothlein R et al. Reduction of central nervous system ischemic injury by monoclonal antibody to intercellular adhesion molecule. J Neurosurg 1991; 75: 623–7.PubMedCrossRefGoogle Scholar
  78. 78.
    Kelly KJ, Williams WJ, Colvin RB et al. Antibody to intercellular adhesion molecule 1 protects the kidney. Proc Natl Acad Sci USA 1994; 91: 812–6.PubMedCrossRefGoogle Scholar
  79. 79.
    Suzuki S, Toledo PL. Monoclonal antibody to intercellular adhesion molecule 1 as an effective protection for liver ischemia and reperfusion injury. Transplant Proc 1993; 25: 3325–7.PubMedGoogle Scholar
  80. 80.
    Terasaki PI, Cecka JM, Lim C et al. Overview. In: Terasaki PI, Cecka JM, eds. Clinical Transplants 1991. Los Angeles: UCLA Tissue Typing Laboratory, 1991: 409–430.Google Scholar
  81. 81.
    Halloran PF, Aprile MA, Farewell V et al. Early function as the principal correlate of graft survival. Transplantation 1988; 46: 223–8.PubMedCrossRefGoogle Scholar
  82. 82.
    Haug CE, Colvin RB, Delmonico FL et al. A phase I trial of immunosuppression with anti-ICAM-1 (CD54) MoAb in renal allograft recipients. Transplantation 1993; 55: 766–72.PubMedCrossRefGoogle Scholar
  83. 83.
    Fischer A, Griscelli C, Blanche S et al. Prevention of graft failure by an anti-HLFA-1 monoclonal antibody in HLA-mismatched bonemarrow transplantation. Lancet 1986; 2: 1058–61.PubMedCrossRefGoogle Scholar
  84. 84.
    Maraninchi D, Mawas C, Stoppa AM et al. Anti LFA1 monoclonal antibody for the prevention of graft rejection after T cell-depleted HLA-matched bone marrow transplantation for leukemia in adults. Bone Marrow Transplant 1989; 4: 147–50.PubMedGoogle Scholar
  85. 85.
    Baume D, Kuentz M, Pico JL et al. Failure of a CD18/anti-LFAl monoclonal antibody infusion to prevent graft rejection in leukemic patients receiving T-depleted allogeneic bone marrow transplantation. Transplantation 1989; 47: 472–4.PubMedCrossRefGoogle Scholar
  86. 86.
    Stoppa AM, Maraninchi D, Blaise D et al. Anti-LFAl monoclonal antibody (25.3) for treatment of steroid-resistant grade III–IV acute graft-versus-host disease. Transpl Int 1991; 4: 3–7.PubMedGoogle Scholar
  87. 87.
    Le Mauff B, Hourmant M, Rougier JP et al. Effect of anti-LFAl (CD 11a) monoclonal antibodies in acute rejection in human kidney transplantation. Transplantation 1991; 52: 291–296.PubMedCrossRefGoogle Scholar
  88. 88.
    Hourmant M, Le Mauff B, Le Meur Y et al. Administration of an anti-CD 11a monoclonal antibody in recipients of kidney transplantation. A pilot study. Transplantation 1994; 58: 377–80.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 1995

Authors and Affiliations

  • John Powelson
  • A. Benedict Cosimi

There are no affiliations available

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