An update on new immunosuppressive drugs undergoing preclinical and clinical trials: Potential applications in organ transplantation

American Journal of Kidney Diseases

Volumn 29, Issue 2, 1997, Pages 303-317

  First, M Roy ^a,b  

^a UNIVERSITY OF CINCINNATI MEDICAL CENTER   (United States)

^b GENZYME CORPORATION   (United States)

Author keywords

immunosuppreseive drugs; Organ transplantation

Indexed keywords

15 DEOXYSPERGUALIN; 2 (3 DIMETHYLAMINOPROPYL) 8,8 DIETHYL 2 AZASPIRO[4.5]DECANE; BREQUINAR; CYCLOSPORIN A; CYCLOSPORIN G; IMMUNOSUPPRESSIVE AGENT; LEFLUNOMIDE; MIZORIBINE; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; NEW DRUG; RAPAMYCIN; TACROLIMUS;

BONE MARROW SUPPRESSION; CLINICAL TRIAL; DRUG INDUCED DISEASE; DRUG RESEARCH; GASTROINTESTINAL SYMPTOM; GRAFT REJECTION; HUMAN; IMMUNOSUPPRESSIVE TREATMENT; KIDNEY TRANSPLANTATION; NEPHROTOXICITY; ORGAN TRANSPLANTATION; POSTOPERATIVE COMPLICATION; REVIEW;

EID: 0030941092     PISSN: 02726386     EISSN: None     Source Type: Journal    
DOI: 10.1016/s0272-6386(97)90046-9     Document Type: Review

References (138)

1. First MR: New immunosuppressive drugs. Am J Kidney Dis 19:3-9, 1992
2. Schroeder TJ, First MR: Monoclonal antibodies in organ transplantation. Am J Kidney Dis 23:138-147, 1994
3. Soulillou P-J: Relevant targets for therapy with monoclonal antibodies in allograft transplantation. Kidney Int 46:540-553, 1994
4. Masroor S, Schroeder TJ, Michler RE, Alexander JW, First MR: Monoclonal antibodies in organ transplantation: An overview. Transplant Immunol 2:176-189, 1994
5. Kahan BD: Synergism: How assessed and how achieved. Clin Transplant 5:534-539, 1991
6. Morris RE: Primer on new small molecule immunosuppressants. Transplant Soc Bull 1:15-21, 1993
7. Rossi SJ, Schroeder TJ, Hariharan S, First MR: Prevention and management of the adverse effects associated with immunosuppressive therapy. Drug Safety 9:104-131, 1993
8. Strom TB, Tilney NL: Immunobiology and immunopharmacology of graft rejection, in Schrier RW, Gottschalk CW (eds): Diseases of the Kidney (ed 5). Boston, MA, Little, Brown, 1993, pp 2879-2910
9. Schreiber SL: Chemistry and biology of the immunophilins and their immunosuppressive ligands. Science 251:283-287, 1991
10. Lu CY, Sicher SC, Vazquez MA: Prevention and treatment of renal allograft rejection: New therapeutic approaches and new insights into established therapies. J Am Soc Nephrol 4:1239-1256, 1993
11. Khanna A, Li B, Stenzel KH, Suthanthiran M: Regulation of new DNA synthesis in mammalian cells by cyclosporine. Demonstration of transforming growth factor β-dependent mechanism of inhibition of cell growth. Transplantation 57:577-582, 1994
12. Kahan BD: Cyclosporine. N Engl J Med 321:1725-1738, 1989
13. First MR: Renal allograft survival after 1 and 10 years: Comparison between pre-cyclosporin and cyclosporin data. Nephrol Dial Transplant 9:90-97, 1993
14. Ptachainski RJ, Burckart GJ, Venkataramanan R: Cyclosporine concentration determinations for monitoring and pharmacokinetic studies. J Clin Pharmacol 26:358-366, 1986
15. Lindholm A, Welsh M, Rutzky L, Kahan BD: The adverse impact of high cyclosporine clearance rates on the incidence of acute rejection and graft loss. Transplantation 55:985-993, 1993
16. Myers B: Cyclosporine nephrotoxicity. Kidney Int 30:964-974, 1986
17. Kahan BD: Cyclosporine nephrotoxicity. Pathogenesis, prophylaxis, therapy, and prognosis. Am J Kidney Dis 8:323-331, 1986
18. Feutren G, Mihatsch MJ: Risk factors for cyclosporine-induced nephropathy in patients with autoimmune disease. N Engl J Med 326:1654-1660, 1992
19. Ritschel WA, Adolph S, Ritschel GB, Schroeder T: Improvement of peroral absorption of cyclosporine A by microemulsions. Methods Find Exp Clin Pharmacol 12:127-134, 1990
20. Kovarik JM, Kallay Z, Mueller EA, van Bree JB, Arns W, Renner E: Acute effect of cyclosporin on renal function following the initial changeover to a microemulsion formulation in stable renal transplant patients. Transplant Int 8:335-339, 1995
21. Vonderscher J, Meinzer A: Rationale for the development of Sandimmune Neoral. Transplant Proc 26:2925-2927, 1994
22. Kahan BD, Dunn J, Fitts C, van Buren D, Wombolt D, Pollak R, Carson R, Alexander JW, Choc M, Wong R, Hwang DS: Reduced inter-and intrasubject variability in cyclosporine pharmacokinetics in renal transplant recipients treated with a microemulation formulation in conjunction with fasting, low fat meals, or high fat meals. Transplantation 59:505-511, 1995
23. Dunn SP, Cooney GF, Kulinsky A, Falkenstein K, Pierson A, Elder CA, Meligeni J: Absorption characteristics of a microemulsion formulation of cyclosporine in de novo pediatric liver transplant recipients. Transplantation 60:1438-1442, 1995
24. Storck M, Mickley V, Grab C, Steinbach G, Abendroth D: Cyclosporine levels in diabetic (type I) patients undergoing kidney or kidney and pancreas transplantation: Role of a new galenic formula. Transplant Proc 26:2996-2998, 1994
25. Fiocchi R, Mamprin F, Gamba A, Glauber M, Catania S, Cattaneo G, Torre L, Bertocchi C, Ruhrmann R, Colombo D: Pharmacokinetic profile of cyclosporin A in long-term heart transplanted patients treated with a new oral formulation. Transplant Proc 26:2994-2995, 1994
26. Neumayer HH, Budde K, Farber L, Haller P, Kohnen R, Maibucher A, Schuster A, Vollmer J, Waiser J, Luft FC: Conversion to microemulsion cyclosporine in stable renal transplant patients: Results after one year. Clin Nephrol 45:326-331, 1996
27. McKenna RM, Szturm K, Jeffrey JR, Rush DN: Inhibition of cytokine production by cyclosporine A and G. Transplantation 47:343-348, 1989
28. Masri MA, Naiem M, Pingle S, Daar AS: Cyclosporine A versus cyclosporine G: A comparative study of survival, hepatotoxicity, nephrotoxicity, and splenic atrophy in BALB/ c mice. Transplant Int 1:13-18, 1988
29. Burdmann EA, Andoh TF, Rosen S, Lindsley J, Munar MY, Elzinga LW, Bennett WM: Experimental nephrotoxicity, hepatotoxicity and pharmacokinetics of cyclosporin G versus cyclosporin A. Kidney Int 45:684-691, 1994
30. Huser B, Thiel G, Oberholzer M, Beveridge T, Bianchi L, Mihatsch MJ, Landmann J: The efficacy and tolerability of cyclosporine G in human kidney transplant recipients. Transplantation 54:65-69, 1992
31. Henry ML, Tesi RJ, Elkhammas EA, Ferguson RM: A randomized, prospective, double-blinded study of cyclosporine vs. OG37-325 in cadaveric renal transplantation - A preliminary report. Transplantation 55:748-752, 1993
32. Thomson AW: FK-506: Profile of an important new immunosuppressant. Transplant Rev 4:1-13, 1990
33. Johansson A, Moller E: Evidence that the immunosuppressive effects of FK-506 and cyclosporine are identical. Transplantation 50:1001-1007, 1990
34. Wood RP, Katz SM, Kahan BD: New immunosuppressive agents. Transplant Sci 1:34-46, 1991
35. Peters DH, Fittow A, Plosker GL, Faulds D: Tacrolimus: A review of its pharmacology and therapeutic potential in hepatic and renal transplantation. Drugs 46:746-794, 1993
36. Bierer BE, Somers PK, Wandless TJ, Burakoff SJ, Schreiber SL: Probing immunosuppressant action with a non-natural ligand. Science 250:556-559, 1990
37. Van Duyne GD, Standaert RF, Karplus PA, Schreiber SL, Clardy J: Atomic structure of FKBP-FK506, an immunophilin-immunosuppressant complex. Science 252:839-842, 1991
38. Suzuki N, Sakane T, Tsunematsu T: Effects of a novel immunosuppressive agent, FK506, on human B cell activation. Clin Exp Immunol 79:240-245, 1990
39. Vathsala A, Goto S, Yoshimura N, Stepkowski S, Chou T-C, Kahan BD: The immunosuppressive antagonism of low doses of FK506 and cyclosporine. Transplantation 52:121-128, 1991
40. Fukuse T, Hirai T, Yokomise H, Hasegawa S, Hirata T, Muro K, Inui K, Hitomi S, Wada H: Combined therapy with FK-506 and cyclosporine for canine lung allotransplantation: Immunosuppressive effects and blood trough levels. J Heart Lung Transplant 12:941-947, 1993
41. Tanabe M, Todo S, Murase N: Combined immunosuppressive therapy with low dose FK506 and antimetabolites in rat allograft heart transplantation. Transplantation 58:23-27, 1994
42. Starzl TE, Fung J, Jordan M, Shapiro R, Tzakis A, McCauley J, Johnston J, Iwaki Y, Jain A, Alessiani M, Todo S: Kidney transplantation under FK 506. JAMA 264:63-67, 1990
43. Japanese FK506 Study Group: FK506: Long-term study in kidney transplantation. Transplant Proc 27:818-821, 1995
44. Schleibner S, Krauss M, Wagner K, Erhard J, Christiaans M, van Hooff J, Buist L, Mayer D: FK506 versus cyclosporin in the prevention of renal allograft rejection - European pilot study: Six-week results. Transplant Int 8:86-90, 1995
45. Laskow DA, Vincenti F, Neylan J, Mendez R, Matas A: Phase II FK506 multicenter concentration control study: One-year follow-up. Transplant Proc 27:809-811, 1995
46. Gjertson DW, Cecka JM, Terasaki PI: The relative effects of FK506 and cyclosporine on short- and long-term kidney graft survival. Transplantation 60:1384-1388, 1995
47. Woodle ES, Thistlethwaite JR, Gordon JH, Laskow D, Deierhoi MH, Burdick JD, Pirsch J, Sollinger H, Vincenti F, Burrows L, Schwartz B, Danovitch GM, Wilkinson AH, Shaffer D, Simpson MA, Freeman RB, Rohrer RJ, Mendez R, Aswad S, Munn SR, Wiesner RH, Delmonico FL, Neylan J, Whelchel J: A multicenter trial of FK506 (tacrolimus) therapy in refractory acute renal allograft rejection: A report of the Tacrolimus Kidney Transplantation Rescue Study Group. Transplantation 62:594-599, 1996
48. Ciancio G, Roth D, Burke G, Nery J, Scantlebury J, Shapiro R, Esquenazi V, Olson L, Gharagozloo H, Miller J: Renal transplantation in a new immunosuppressive era. Transplant Proc 27:812-813, 1995
49. European FK506 Multicentre Liver Study Group: Randomized trial comparing tacrolimus (FK506) and cyclosporin in prevention of liver allograft rejection. Lancet 334:423-428, 1994
50. The US Multicenter FK506 Liver Study Group: A comparison of tacrolimus (FK506) and cyclosporine for immunosuppression in liver transplantation. N Engl J Med 331:1110-1115, 1994
51. Lake JR, Gorman KJ, Esquivel CO, Wiesner RH, Klintmalm GB, Miller CM, Shaw BW, Gordon JA: The impact of immunosuppressive regimens on the cost of liver transplantation - Results from the U.S. FK506 multicenter trial. Transplantation 60:1089-1095, 1995
52. Manez R, Jain A, Marino IR, Thomson AW: Comparative evaluation of tacrolimus (FK506) and cyclosporin A as immunosuppressive agents. Transplant Rev 9:63-76, 1995
53. McDiarmid SV, Colonna JO, Snaked A: A comparison of renal function in cyclosporine- and FK-506-treated patients after primary orthotopic liver transplantation. Transplantation 56:847-853, 1993
54. Platz K-P, Mueller AR, Blumhardt G: Nephrotoxicity following orthotopic liver transplantation: A comparison between cyclosporine and FK506. Transplantation 58:170-178, 1994
55. Demetris AJ, Banner B, Fung J, Shapiro R, Jordan M, Starzl TE: Histopathology of human renal allograft rejection under FK506: A comparison with cyclosporine. Transplant Proc 23:944-946, 1991
56. Japanese FK506 Study Group: Japanese study of FK506 on kidney transplantation: Results of a late phase II study. Transplant Proc 25:649-654, 1993
57. Klintmalm G: A review of FK506: A new immunosuppressant agent for the prevention and rescue of graft rejection. Transplant Rev 8:53-63, 1994
58. Holman MJ, Gonwa TA, Cooper B: FK506-associated thrombotic thrombocytopenic purpura. Transplantation 55:205-206, 1993
59. Eidelman BH, Abu-Elmagd K, Wilson J, Fung JJ, Alessiani M, Jain S, Takaya S, Todo SN, Tzakis A, Van Thiel D, Shannon W, Starzl TE: Neurologic complications of FK506. Transplant Proc 23:3175-3178, 1991
60. Mueller AR, Platz K-P, Bechstein W-O: Neurotoxicity after orthotopic liver transplantation: A comparison between cyclosporine and FK506. Transplantation 58:155-170, 1994
61. Krentz AJ, Dmitrewski J, Mayer D: Postoperative glucose metabolism in liver transplant recipients: A two-year randomized prospective study of cyclosporine versus FK506. Transplantation 57:1666-1669, 1994
62. Carroll PB, Boschero AC, Li M-Y, Tzakis AG, Starzl TE, Atwater L: Effect of the immunosuppressant FK506 on glucose-induced insulin secretion from adult rat islets of Langerhans. Transplantation 51:275-278, 1991
63. Hadley S, Samore MH, Lewis WD, Jenkins RL, Karchmer AW, Hammer SM: Major infectious complications after orthotopic liver transplantation and comparison of outcomes in patients receiving cyclosporine or FK506 as primary immunosuppression. Transplantation 59:851-859, 1995
64. Tzakis AG, Reyes J, Todo S: Two-year experience with FK506 in pediatric patients. Transplant Proc 25:619-621, 1993
65. Atkison P, Joubert G, Barron A, Grant D, Paradis K, Seidman E, Wall W, Rosenberg H, Howard J, Williams S, Stiller C: Hypertrophic cardiomyopathy associated with tacrolimus in pediatric transplant patients. Lancet 345:894-896, 1995
66. Morris RE: Rapamycins: Antifungal, antitumor, antiproliferative and immunosuppressive macrolides. Transplant Rev 6:39-87, 1992
67. Kahan BD, Chang JY, Sehgal SN: Preclinical evaluation of a new potent immunosuppressive agent, rapamycin. Transplantation 52:185-191, 1991
68. Dumont FJ, Staruch MJ, Koprak SL, Melino MR, Sigal NH: Distinct mechanism of suppression of murine T cell activation by the related macrolides FK-506 and rapamycin. J Immunol 144:251-258, 1990
69. Daloze P, Chen H, Luo H, Xu D, Wu J: Rapamycin's long-term effect on humoral and cellular immune responses in the rat. Transplant Proc 25:721-722, 1993
70. Chung J, Kuo CJ, Crabtree GR, Blenis J: Rapamycin-FKBP specifically blocks growth-dependent activation of and signaling by the 70 kd S6 protein kinases. Cell 69:1227-1236, 1992
71. Lai JH, Tan H: CD28 signaling causes a sustained down-regulation of I kappa B alpha which can be prevented by the immunosuppressant rapamycin. J Biol Chem 269:30077-30080, 1994
72. Kimball PM, Kerman RH, Kahan BD: Production of synergistic but nonidentical mechanisms of immunosuppression by rapamycin and cyclosporine. Transplantation 51:486-490, 1991
73. Zheng XX, Strom TB, Steele AW: Quantitative comparison of rapamycin and cyclosporine effects on cytokine gene expression studied by reverse transcriptase-competitive polymerase chain reaction. Transplantation 58:87-92, 1994
74. Boyle MJ, Kahan BD: Immunosuppressive role of rapamycin in allograft rejection, in Thomson AW, Starzl TE (eds): Immunosuppressive Drugs: Developments in Anti-rejection Therapy. London, UK, Edward Arnold, 1994, pp 129-140
75. Hartner WC, Van der Werf WA, Lodge JPA, Gilchrist B, De Fazio SR, Markees TG, Yatko C, Monaco AP, Gozzo JJ: Effect of rapamycin on renal allograft survival in canine recipients treated with antilymphocyte serum, donor bone marrow, and cyclosporine. Transplantation 60:1347-1374, 1995
76. Meiser BM, Billingham ME, Morris RE: Effects of cyclosporine, FK506 and rapamycin on graft vessel disease. Lancet 338:1297-1298, 1991
77. Gregory CR, Pratt RE, Huie P, Shorthouse R, Dzau VJ, Billingham ME, Morris RE: Effect of treatment with cyclosporine, FK506, rapamycin, mycophenolic acid or deoxyspergualin on vascular muscle proliferation in vitro and in vivo. Transplant Proc 25:770-771, 1993
78. Whiting PH, Woo J, Adam BJ, Hasan NU, Davidson RJ, Thomson AW: Toxicity of rapamycin: A comparative and combination study with cyclosporine at immunotherapeutic doses in the rat. Transplantation 52:203-208, 1991
79. DiJoseph JF, Mihatsch MJ, Sehgal SN: Renal effects of rapamycin in the spontaneously hypertensive rat. Transplant Int 7:83-88, 1994
80. Sehgal SN, Camardo JS, Scarola JA, Maida BT: Rapamycin (sirolimus, rapamune). Curr Opin Nephrol Hypertens 4:482-487, 1995
81. Murgia MG, Jordan S, Kahan BD: The side effect profile of sirolimus: A phase I study in quiescent cyclosporine-prednisone-treated renal transplant patients. Kidney Int 49:209-216, 1996
82. Williams JW, Xiao F, Foster PF, Chong A, Sharma S, Bartlett R, Sankarg HN: Immunosuppressive effects of leflunomide in a cardiac allograft model. Transplant Proc 25:745-746, 1993
83. Chong AS-F, Finnegan A, Jiang XL, Gebel H, Sankarg HN, Foster P, Williams JW: Leflunomide, a novel immunosuppressive agent: The mechanism of inhibition of T cell proliferation. Transplantation 55:1361-1366, 1993
84. Kuchle CCA, Thoenes GH, Langer KH, Schorlemmer HU, Bartlett RR: Prevention of kidney and skin allograft rejection in rats by leflunomide, a new immunosuppressive agent. Transplant Proc 23:1083-1086, 1991
85. Morris RE: Mechanism of action of new immunosuppressive drugs. Kidney Int 49:826-38, 1996
86. McChesney LP, Xiao F, Sankary HN: An evaluation of leflunomide in the canine renal transplantation model. Transplantation 57:1717-1722, 1994
87. Morris R, Huang X, Cao W, Zheng B, Shorthouse RA: Leflunomide (HWA 486), its analogs suppress T and B cell proliferation in vitro, acute rejection, ongoing rejection, ongoing rejection and anti-donor antibody synthesis in mouse, rat and cynomolgus monkey transplant recipients, as well as arterial intimai thickening after balloon injury. Transplant Proc 27:445-447, 1995
88. Turka LA, Dayton J, Sinclair G, Thompson CB, Mitchell BS: Guanine ribonucleotide depletion inhibits T cell activation: Mechanism of action of the immunosuppressive drug mizoribine. J Clin Invest 87:940-948, 1991
89. Hayashi R, Suzuki S, Shimatani K, Watanabe H, Kenmochi T, Fukuoka T, Niiya S, Amemiya H: Synergistic effect of cyclosporine and mizoribine on graft survival in canine organ transplantation. Transplant Proc 22:1676-1678, 1990
90. Mita K, Akiyama N, Nagao T, Sugimoto H, Inoue S, Osakabe T, Nakayama Y, Yakota K: Advantages of mizoribine over azathioprine combination therapy with cyclosporine for renal transplantation. Transplant Proc 22:1679-1681, 1990
91. Kokado Y, Ishibahi M, Jiang H, Takahara S, Sonoda T: Low-dose ciclosporin, mizoribine and prednisolone in renal transplantation: A new triple-drug therapy. Clin Transplant 4:191-197, 1990
92. Lee HA, Slapak M, Venkatraman G, Mason J, Digard N, Wise M: Mizoribine as an alternative to azathioprine in triple-therapy immunosuppressant regimens in cadaveric renal transplantation. Transplant Proc 25:2699-2700, 1993
93. Gregory CR, Gourley IM, Cain GR, Patz JD, Imondi KA, Martin JA: Mizoribine serum levels associated with enterotoxicity in the dog. Transplantation 51:877-881, 1991
94. Morris RE, Hoyt EG, Murphy MP: Mycophenolic acid morpholinoethylester (RS-61443) is a new immunosuppressant that prevents and halts heart allograft rejection by selective inhibition of T- and B-cell purine synthesis. Transplant Proc 22:1659-1662, 1990
95. Allison AC, Eugui EM, Sollinger HW: Mycophenolate mofetil (RS-61443): Mechanisms of action and effects in transplantation. Transplant Rev 7:129-139, 1993
96. Sollinger HW, Eugui EM, Allison AC: RS-61443: Mechanism of action, experimental and early clinical results. Clin Transplant 5:523-526, 1991
97. Eugui EM, Almquist SJ, Muller CD, Allison AC: Lymphocyte-selective cytostatic and immunosuppressive effects of mycophenolic acid in vitro: Role of deoxyguanosine nucleotide depletion. Scand J Immunol 33:161-173, 1991
98. Hao L, Lafferty KJ, Allison AC, Eugui EM: RS-61443 allows islet allografting and specific tolerance in mice. Transplant Proc 22:876-879, 1990
99. Deierhoi MH, Kauffman RS, Hudson SL, Barber WH, Curtis JJ, Julian BA, Gaston RS, Laskow DA, Diethelm AG: Experience with mycophenolate mofetil (RS61443) in renal transplantation at a single center. Ann Surg 217:476-484, 1993
100. Sollinger HW, for the US Renal Transplant Mycophenolate Mofetil Study Group: Mycophenolate mofetil for the prevention of acute rejection in primary cadaveric renal allograft recipients. Transplantation 60:225-232, 1995
101. European Mycophenolate Mofetil Cooperative Study Group: Placebo-controlled study of mycophenolate mofetil combined with cyclosporin and corticosteroids for prevention of acute rejection. Lancet 345:1321-1325, 1995
102. Tricontinental Mycophenolate Mofetil Renal Transplantation Study Group: A blinded, randomized clinical trial of mycophenolate mofetil for the prevention of acute rejection in cadaveric renal transplantation. Transplantation 61:1029-1037, 1996
103. The Mycophenolate Mofetil Renal Refractory Rejection Study Group: Mycophenolate mofetil for the treatment of refractory, acute, cellular renal transplant rejection. Transplantation 61:722-729, 1996
104. Klintmalm GB, Ascher NL, Busuttil RW, Deierhoi M, Gonwa TA, Kauffman R, McDiarmid S, Poplawski S, Sollinger H, Roberts J: RS-61443 for treatment-resistant human liver rejection. Transplant Proc 25:697, 1993
105. Simon P, Townsend RM, Harris RR, Jones EA, Jaffe BD: Brequinar sodium: Inhibition of dihydrorotic acid dehydrogenase, depletion of pyrimidine pools, and consequent inhibition of immune functions in vitro. Transplant Proc 25:77-80, 1993 (suppl 2)
106. Makowka L, Cramer DV: Brequinar sodium: A new immunosuppressive drug for transplantation. Transplant Sci 2:50-54, 1992
107. Cramer DV, Chapman FA, Jaffee BD, Jones EA, Knoop M, Hreha-Eiras G, Makokwa L: The effect of a new immunosuppressive drug, brequinar sodium, on heart, liver, and kidney allograft rejection in the rat. Transplantation 53:303-308, 1992
108. Collins BH, Areford ML, Fabian MA, Jaffee BD, Bollinger RR: Brequinar sodium potentiates the effects of cyclosporine in experimental small bowel transplantation. Transplant Proc 25:37-39, 1993 (suppl 2)
109. Kahan BD, Tejpal N, Gibbons-Stubbers S: The synergistic interactions in vitro and in vivo of brequinar sodium with cyclosporine or rapamycin alone and in triple combination. Transplantation 55:894-900, 1993
110. Hullett DA, Sollinger HW: Mycophenolate mofetil and brequinar sodium: New immunosuppressive agents. Transplant Proc 25:45-47, 1993 (suppl 2)
111. Yasunaga C, Cramer DV, Cosenz CA, Tuso PJ, Chapman FA, Barnett M, Wu GD, Putnam BA, Makowka L: Effect of brequinar sodium on in vivo antibody production. Transplant Proc 25:40-44, 1993 (suppl 2)
112. Reichenspurner H, Hildebrandt A, Human PA, Boehm DH, Rose AG, Odell JA, Reichert B, Schorlemmer HU: 15-Deoxyspergualin for induction of graft nonreactivity after cardiac and renal allotransplantation in primates. Transplantation 50:181-185, 1990
113. Valdivia LA, Monden M, Gotoh M, Nakano Y, Tono T, Mon T: Evidence that deoxyspergualin prevents sensitization and first-set cardiac xenograft rejection in rats by suppression of antibody formation. Transplantation 50:132-136, 1990
114. Kaufman DB, Gores PF, Kelley S, Grasela DM, Nadler SG, Ramos E: 15-Deoxyspergualin: Immunotherapy in solid organ and cellular transplantation. Transplant Rev 10:160-174, 1996
115. Yabuuchi H, Nakajima Y, Segawa M, Kanehiro H, Murao Y, Hisanaga M, Yoshimura A, Wada T, Nakagawa K, Nakano H: Prominent prolongation of islet xenograft survival in combination therapy with FK 506 and 15-deoxyspergualin. Transplant Proc 23:859-861, 1991
116. Yano K, Fukado Y, Sumimoto R, Sumimoto K, Ito H, Dohi K: Suppression of liver allograft rejection by administration of 15-deoxyspergualin: Comparison of administration via the hepatic artery, portal vein, or systemic circulation. Transplant Int 7:149-156, 1994
117. Raisanen-Sokolowski A, Yilmaz S, Tufveson G, Hayry P: Partial inhibition of allograft arteriosclerosis (chronic rejection) by 15-deoxyspergualin. Transplantation 57:1772-1777, 1994
118. Nadler SG, Tepper MA, Schacter B, Mazzucco CE: Interaction of the immunosuppressant deoxyspergualin with a member of the HSP 70 family of heat shock proteins. Science 258:484-486, 1986
119. Koyama I, Amemiya H, Taguchi Y, Wanatage T, Nagashima N, Suzuki S, Omoto R: Prophylactic use of deoxyspergualin in a quadruple immunosuppressive protocol in renal transplantation. Transplant Proc 23:1096-1098, 1991
120. Okazaki H, Sato T, Amada N: Further study of deoxyspergualin prophylaxis in living related renal transplantation. Transplant Proc 25:772-773, 1993
121. Amemiya H, Taguchi Y, Fukao K, Isono K, Omato R, Ota K, Kosaki M, Takagi H, Oka T, Sonoda T, Orita K, Dohi K: Establishment of rejection therapy with deoxyspergualin by multicentral controlled clinical studies in renal recipients. Transplant Proc 25:730-733, 1993
122. Ohlman S, Zilg H, Schindel F, Lindholm A: Pharmacokinetics of 15-deoxyspergualin studied in renal transplant patients receiving the drug during graft rejection. Transplant Int 7:5-10, 1994
123. Groth CG, Ohlman S, Ericzon BG, Barkholt L, Reinholt FP: Deoxyspergualin for liver graft rejection. Lancet 336:626, 1990
124. Matas AJ, Gores PK, Kelley SL, Bielefield-Skrokov M, Kinaszezuk M, Gruessner RWG, Najarian JS: Pilot evaluation of 15-deoxyspergualin for refractory acute renal transplant rejection. Clin Transplant 8:116-119, 1994
125. Groth CF: Deoxyspergualin in allogeneic kidney and xenogeneic islet transplantation: Early clinical trials. Ann N Y Acad Sci 685:193-195, 1993
126. Gores PF, Najarian JF, Stephanian E, Lloveras JJ, Kelley SL, Sutherland DE: Insulin independence in type I diabetes after transplantation of unpurified islets from single donor with 15-deoxyspergualin. Lancet 341:19-21, 1993
127. Imamura M, Han M, Hashino S: In vivo effects of the immunosuppressant 15-deoxyspergualin on hematopoiesis in murine allogeneic bone marrow chimeras. Transplantation 58:214-223, 1994
128. Badger AM, King AG, Talmadge JE, Schwartz DA, Picker DH, Mirabelli CK, Hanna N: Induction of non-specific suppressor cells in normal Lewis rats by a novel azaspirane SK&F 105685. J Autoimmun 3:485-500, 1990
129. Schmidbauer G, Hancock WW, Badger AM, Kupiec-Weglinski JW: Induction of nonspecific x-irradiation-resistant suppressor cell activity in vivo and prolongation of vascularized allograft survival by SK&F 105685, a novel immunomodulatory azaspirane. Transplantation 55:1236-1243, 1993
130. Fan P-Y, Albrightson CR, Howell DN, Best C, Badger AM, Coffman TM: The azaspirane SKF 105685 ameliorates renal allograft rejection in rats. J Am Soc Nephrol 3:1680-1685, 1993
131. Sayegh MH, Turka LA: T cell costimulatory pathways: Promising novel targets for immunosuppression and tolerance induction. J Am Soc Nephrol 6:1143-1150, 1995
132. Allison JP, Krummel MF: The ying and yang of T cell costimulation. Science 270:932-933, 1995
133. Schwartz RH: T-cell anergy. Sci Am 269:62-71, 1993
134. Linsley PS, Brady W, Urnes M, Grosmaire LS, Damle NK, Ledbetter JA: CTLA-4 is a second receptor for the B cell activation antigen BT. J Exp Med 174:561-569, 1991
135. Sayegh MH, Watschinger B, Carpenter CB: Mechanisms of T cell recognition of alloantigen: The role of peptides. Transplantation 57:1295-1302, 1994
136. Krensky AM, Lyn SC, Pouletty P, Benjamin R, Parnam P, Clayberger C: Peptides corresponding to the CD8 binding region of HLA class I block the differentiation of cytotoxic T lymphocytes precursors. Transplant Proc 25:483-484, 1993
137. Sayegh MH, Khoury SK, Hancock WW, Weiner HL, Carpenter CB: Induction of immunity and oral tolerance with polymorphic class II MHC allopeptides in the rat. Proc Natl Acad Sci U S A 89:7762-7766, 1992
138. Nisco S, Vriens P, Hoyt G, Lyu SC, Fartan F, Pouletty P, Krensky AM, Clayberger C: Induction of allograft tolerance in rats by an HLA derived peptide and cyclosporin A. J Immunol 152:3786-3792, 1994