Molecular targets for existing and novel immunosuppressive drugs

Expert Reviews in Molecular Medicine

Volumn 2, Issue 4, 2000, Pages 1-23

  Stepkowski, Stanislaw M ^a  

^a UNIVERSITY OF TEXAS MEDICAL SCHOOL   (United States)

Author keywords

15 deoxyspergualin; allograft rejection; antiproliferative agents; antisense oligodeoxynucleotides; antisense technology; brequinar; cyclosporine A; FTY720; immunosuppression; immunosuppressive drugs; leflunomide; mycophenolate mofetil; sirolimus; tacrolimus

Indexed keywords

EID: 85012553495     PISSN: 14623994     EISSN: 14623994     Source Type: Journal    
DOI: 10.1017/S1462399400001769     Document Type: Article

References (139)

1. Elion, G.B., Burgi, E. and Hitchings, G.H. (1952) Studies on condensed pyrimidine systems. IX. Synthesis of some 6-substituted purines. J Am Chem Soc 74, 411–414
2. Murray, J.E. et al. (1963) Prolonged survival of human-kidney homografts by immunosuppressive drug therapy. N Engl J Med 268, 1315–1323
3. Bach, J.F. (1975) The mode of action of immunosuppressive agents. Front Biol 41, 1–374, PubMed ID: 79025214
4. Gosio, B. (1996) Ricerche bacteriologiche e chimiche sulle alterazioni del mais. Riv Ig Sanita Publica Ann 7, 825
5. Platz, K.P. et al. (1991) RS-61443 - a new, potent immunosuppressive agent. Transplantation 51, 27–31, PubMed ID: 91102816
6. Dayton, J.S. et al. (1994) Effects of human T lymphocyte activation on inosine monophosphate dehydrogenase expression. J Immunol 152, 984–991, PubMed ID: 94132651
7. Eugui, E.M. et al. (1991) Lymphocyte-selective cytostatic and immunosuppressive effects of mycophenolic acid in vitro: role of deoxyguanosine nucleotide depletion. Scand J Immunol 33, 161–173, PubMed ID: 91205230
8. Sollinger, H.W. et al. (1992) RS-61443 - a phase I clinical trial and pilot rescue study. Transplantation 53, 428–432, PubMed ID: 92151327
9. Deierhoi, M.H. et al. (1993) Experience with mycophenolate mofetil (RS61443) in renal transplantation at a single center. Ann Surg 217, 476–482; discussion 482–474, PubMed ID: 93256640
10. Weber, L.T. et al. (1998) Pharmacokinetics of mycophenolic acid (MPA) and determinants of MPA free fraction in pediatric and adult renal transplant recipients. German Study group on Mycophenolate Mofetil Therapy in Pediatric Renal Transplant Recipients. J Am Soc Nephrol 9, 1511–1520, PubMed ID: 98361140
11. Kirklin, J.K. et al. (1994) Treatment of recurrent heart rejection with mycophenolate mofetil (RS- 61443): initial clinical experience. J Heart Lung Transplant 13, 444–450, PubMed ID: 94339147
12. European Mycophenolate Mofetil Cooperative Study Group (1995) Placebo-controlled study of mycophenolate mofetil combined with cyclosporin and corticosteroids for prevention of acute rejection. Lancet 345, 1321–1325, PubMed ID: 95272240
13. Sollinger, H.W. (1995) Mycophenolate mofetil for the prevention of acute rejection in primary cadaveric renal allograft recipients. U.S. Renal Transplant Mycophenolate Mofetil Study Group. Transplantation 60, 225–232, PubMed ID: 95372938
14. Schmid, C. et al. (1995) Comparison of rapamycin, RS 61443, cyclosporine, and low-dose heparin as treatment for transplant vasculopathy in a rat model of chronic allograft rejection. Transplant Proc 27, 438–439, PubMed ID: 95184692
15. Halloran, P. et al. (1997) Mycophenolate mofetil in renal allograft recipients: a pooled efficacy analysis of three randomized, double-blind, clinical studies in prevention of rejection. The International Mycophenolate Mofetil Renal Transplant Study Groups [published erratum appears in Transplantation 1997 Feb 27; 63(4): 618].
16. Transplantation 63, 39–47, PubMed ID: 97153368
17. Jain, A.B. et al. (1998) A prospective randomized trial of tacrolimus and prednisone versus tacrolimus, prednisone, and mycophenolate mofetil in primary adult liver transplant recipients: an interim report. Transplantation 66, 1395–1398, PubMed ID: 99060964
18. Dexter, D.L. et al. (1985) Activity of a novel 4-quinolinecarboxylic acid, NSC 368390 [6-fluoro-2- (2'-fluoro-1,1'-biphenyl-4-yl)-3-methyl-4-quinolinecarb oxylic acid sodium salt], against experimental tumors. Cancer Res 45, 5563–5568, PubMed ID: 86027861
19. Simon, P. et al. (1993) Brequinar sodium: inhibition of dihydroorotic acid dehydrogenase, depletion of pyrimidine pools, and consequent inhibition of immune functions in vitro. Transplant Proc 25, 77–80, PubMed ID: 93297015
20. Chen, J.J. and Jones, M.E. (1976) The cellular location of dihydroorotate dehydrogenase: relation to de novo biosynthesis of pyrimidines. Arch Biochem Biophys 176, 82–90, PubMed ID: 77020583
21. Cramer, D.V. et al. (1992) The effect of a new immunosuppressive drug, brequinar sodium, on heart, liver, and kidney allograft rejection in the rat. Transplantation 53, 303–308, PubMed ID: 92151305
22. Cramer, D.V. et al. (1992) The prolongation of concordant hamster-to-rat cardiac xenografts by brequinar sodium. Transplantation 54, 403–408, PubMed ID: 93032149
23. Shen, H.S. et al. (1988) Distribution of the novel anticancer drug candidate Brequinar sodium (DuP 785, NSC 368390) into normal and tumor tissues of nude mice bearing human coloncarcinoma xenografts. Cancer Chemother Pharmacol 22, 183–186, PubMed ID: 88311345
24. Barnes, T.B. et al. (1993) Toxicological and pharmacokinetic effects following coadministration of brequinar sodium and cyclosporine to Sprague-Dawley rats. Transplant Proc 25, 71–74, PubMed ID: 93297013
25. Kahan, B.D. et al. (1993) The synergistic interactions in vitro and in vivo of brequinar sodium with cyclosporine or rapamycin alone and in triple combination. Transplantation 55, 894–900, PubMed ID: 93235301
26. Stepkowski, S.M. et al. (1994) Synergistic interactions of cyclosporine, rapamycin, and brequinar on heart allograft survival in mice. Transplant Proc 26, 3025–3027, PubMed ID: 95027293
27. Kawamura, T. et al. (1993) Enhancement of allograft survival by combination RS-61443 and DUP-785 therapy. Transplantation 55, 691–694; discussion 694–695, PubMed ID: 93235262
28. Arteaga, C.L. et al. (1989) Phase I clinical and pharmacokinetic trial of Brequinar sodium (DuP 785; NSC 368390). Cancer Res 49, 4648–4653, PubMed ID: 89303902
29. Maroun, J. et al. (1993) Multicenter phase II study of brequinar sodium in patients with advanced lung cancer. Cancer Chemother Pharmacol 32, 64–66, PubMed ID: 93215035
30. Bartlett, R.R. and Schleyerbach, R. (1985) Immunopharmacological profile of a novel isoxazol derivative, HWA 486, with potential antirheumatic activity - I. Disease modifying action on adjuvant arthritis of the rat. Int J Immunopharmacol 7, 7–18, PubMed ID: 85206488
31. Ogawa, T. et al. (1990) Effects of leflunomide on glomerulonephritis induced by antibasement membrane antibody in rats. Agents Actions 31, 321–328, PubMed ID: 91196658
32. Popovic, S. and Bartlett, R.R. (1987) The use of the murine chronic graft vs host (CGVH) disease, a model for systemic lupus erythematosus (SLE), for drug discovery. Agents Actions 21, 284–286, PubMed ID: 88073525
33. Thoenes, G.H. et al. (1989) Leflunomide (HWA 486) inhibits experimental autoimmune tubulointerstitial nephritis in rats. Int J Immunopharmacol 11, 921–929, PubMed ID: 90129496
34. McChesney, L.P. et al. (1994) An evaluation of leflunomide in the canine renal transplantation model. Transplantation 57, 1717–1722, PubMed ID: 94287458
35. Bartlett, R.R. et al. (1991) Leflunomide (HWA 486), a novel immunomodulating compound for the treatment of autoimmune disorders and reactions leading to transplantation rejection. Agents Actions 32, 10–21, PubMed ID: 91281538
36. Siemasko, K. et al. (1998) Inhibition of JAK3 and STAT6 tyrosine phosphorylation by the immunosuppressive drug leflunomide leads to a block in IgG1 production. J Immunol 160, 1581–1588, PubMed ID: 98129315
37. Schuna, A.A. and Megeff, C. (2000) New drugs for the treatment of rheumatoid arthritis. Am J Health Syst Pharm 57, 225–234, PubMed ID: 20137241
38. Borel, J.F. et al. (1976) Biological effects of cyclosporin A: a new antilymphocytic agent. Agents Actions 6, 468–475, PubMed ID: 76274842
39. Kahan, B.D. et al. (1985) Clinical and experimental studies with cyclosporine in renal transplantation. Surgery 97, 125–140, PubMed ID: 85115949
40. Liu, J. et al. (1991) Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes. Cell 66, 807–815, PubMed ID: 91347380
41. Calne, R.Y. et al. (1978) Cyclosporin A in patients receiving renal allografts from cadaver donors. Lancet 2, 1323–1327, PubMed ID: 79071876
42. Reitz, B.A. et al. (1981) Orthotopic heart and combined heart and lung transplantation with cyclosporin-A immune suppression. Transplant Proc 13, 393–396, PubMed ID: 81276105
43. Starzl, T.E. et al. (1981) Liver transplantation with use of cyclosporin a and prednisone. N Engl J Med 305, 266–269, PubMed ID: 81220857
44. Saunders, N.R. et al. (1984) Cyclosporin and bronchial healing in canine lung transplantation. J Thorac Cardiovasc Surg 88, 993–999, PubMed ID: 85059462
45. Mihatsch, M.J. et al. (1998) The side-effects of ciclosporine-A and tacrolimus. Clin Nephrol 49, 356–363, PubMed ID: 98359620
46. O'Garra, A. et al. (1986) Effects of cyclosporine on responses of murine B cells to T cell- derived lymphokines. J Immunol 137, 2220–2224, PubMed ID: 87009863
47. Tian, L. et al. (1997) Cytokine mRNA expression in tolerant heart allografts after immunosuppression with cyclosporine, sirolimus or brequinar. Transpl Immunol 5, 189–198, PubMed ID: 98066305
48. Khanna, A. et al. (1994) Regulation of new DNA synthesis in mammalian cells by cyclosporine. Demonstration of a transforming growth factor beta-dependent mechanism of inhibition of cell growth. Transplantation 57, 577–582, PubMed ID: 94160338
49. Kino, T. et al. (1987) FK-506, a novel immunosuppressant isolated from a Streptomyces. I. Fermentation, isolation, and physico-chemical and biological characteristics. J Antibiot (Tokyo) 40, 1249–1255, PubMed ID: 88058491
50. Harding, M.W. et al. (1989) A receptor for the immunosuppressant FK506 is a cis-trans peptidyl-prolyl isomerase. Nature 341, 758–760, PubMed ID: 90015223
51. European FK506 Multicentre Liver Study Group (1994) Randomised trial comparing tacrolimus (FK506) and cyclosporin in prevention of liver allograft rejection. Lancet 344, 423–428, PubMed ID: 94335400
52. The U.S. Multicenter FK506 Liver Study Group (1994) A comparison of tacrolimus (FK 506) and cyclosporine for immunosuppression in liver transplantation. N Engl J Med 331, 1110–1115, PubMed ID: 95021534
53. Morris-Stiff, G. et al. (1998) Conversion of renal transplant recipients from cyclosporin to low-dose tacrolimus for refractory rejection. Transpl Int 11, S78–81, PubMed ID: 98329652
54. Klintmalm, G.B. et al. (1993) Use of Prograf (FK 506) as rescue therapy for refractory rejection after liver transplantation (US Multicenter FK 506 Liver Study Group). Transplant Proc 25, 679–688, PubMed ID: 93174708
55. Armitage, J.M. et al. (1991) A clinical trial of FK 506 as primary and rescue immunosuppression in cardiac transplantation. Transplant Proc 23, 1149–1152, PubMed ID: 91111507
56. McMaster, P. and Dousset, B. (1992) The improved results of liver transplantation. Transpl Int 5, 125–128, PubMed ID: 92384807
57. Japanese FK 506 Study Group (1993) Japanese study of FK 506 on kidney transplantation: results of late phase II study. Transplant Proc 25, 649–654, PubMed ID: 93174698
58. Vezina, C., Kudelski, A. and Sehgal, S.N. (1975) Rapamycin (AY-22,989), a new antifungal antibiotic. I. Taxonomy of the producing streptomycete and isolation of the active principle. J Antibiot (Tokyo) 28, 721–726, PubMed ID: 76046040
59. Douros, J. and Suffness, M. (1981) New antitumor substances of natural origin. Cancer Treat Rev 8, 63–87, PubMed ID: 81234410
60. Eng, C.P., Sehgal, S.N. and Vezina, C. (1984) Activity of rapamycin (AY-22,989) against transplanted tumors. J Antibiot (Tokyo) 37, 1231–1237, PubMed ID: 85054260
61. Kahan, B.D. (1993) Immunosuppressive agents acting upon lymphokine synthesis and signal transduction. Clin Transplant 7, 113–125
62. Kunz, J. et al. (1993) Target of rapamycin in yeast, TOR2, is an essential phosphatidylinositol kinase homolog required for G1 progression. Cell 73, 585–596, PubMed ID: 93258821
63. Kuo, C.J. et al. (1992) Rapamycin selectively inhibits interleukin-2 activation of p70 S6 kinase. Nature 358, 70–73, PubMed ID: 92310573
64. Morice, W.G. et al. (1993) Rapamycin-induced inhibition of p34cdc2 kinase activation is associated with G1/S-phase growth arrest in T lymphocytes. J Biol Chem 268, 3734–3738, PubMed ID: 93155234
65. Stepkowski, S.M. et al. (1996) Effects of the pharmacokinetic interaction between orally administered sirolimus and cyclosporine on the synergistic prolongation of heart allograft survival in rats. Transplantation 62, 986–994, PubMed ID: 97032619
66. Stepkowski, S.M. et al. (1991) Rapamycin, a potent immunosuppressive drug for vascularized heart, kidney, and small bowel transplantation in the rat. Transplantation 51, 22–26, PubMed ID: 91102806
67. Kimball, P.M., Kerman, R.H. and Kahan, B.D. (1991) Rapamycin and cyclosporine produce synergistic but nonidentical mechanisms of immunosuppression. Transplant Proc 23, 1027–1028, PubMed ID: 91111460
68. Ochiai, T. et al. (1993) Effects of rapamycin in experimental organ allografting. Transplantation 56, 15–19, PubMed ID: 93325078
69. Murgia, M.G., Jordan, S. and Kahan, B.D. (1996) The side effect profile of sirolimus: a phase I study in quiescent cyclosporine-prednisone-treated renal transplant patients. Kidney Int 49, 209–216, PubMed ID: 96366855
70. Kahan, B.D. et al. (1998) Immunosuppressive effects and safety of a sirolimus/cyclosporine combination regimen for renal transplantation. Transplantation 66, 1040–1046, PubMed ID: 99023675
71. Kahan, B.D. et al. (1999) Sirolimus reduces the incidence of acute rejection episodes despite lower cyclosporine doses in caucasian recipients of mismatched primary renal allografts: a phase II trial. Rapamune Study Group. Transplantation 68, 1526–1532, PubMed ID: 20055895
72. Podder, H. et al. (1999) Sirolimus overcomes rejection factors associated with African-American race. American Society of Transplantation Surgeons, 25th Annual Scientific Meeting, Abstract 166
73. Adams, D.H., Wyner, L.R. and Karnovsky, M.J. (1993) Cardiac graft arteriosclerosis in the rat. Transplant Proc 25, 2071–2073, PubMed ID: 93227449
74. Gregory, C.R. et al. (1995) Treatment with rapamycin and mycophenolic acid reduces arterial intimal thickening produced by mechanical injury and allows endothelial replacement. Transplantation 59, 655–661, PubMed ID: 95193060
75. Wang, M.E. et al. (1992) Evidence that rapamycin rescue therapy delays rejection of major (MHC) plus minor (non-MHC) histoincompatible heart allografts in rats. Transplantation 54, 704–709, PubMed ID: 93032212
76. Chen, H. et al. (1993) Reversal of ongoing heart, kidney, and pancreas allograft rejection and suppression of accelerated heart allograft rejection in the rat by rapamycin. Transplantation 56, 661–666, PubMed ID: 94025076
77. Madsen, J.C. et al. (1998) Transplantation tolerance prevents cardiac allograft vasculopathy in major histocompatibility complex class I-disparate miniature swine. Transplantation 65, 304–313, PubMed ID: 98143273
78. Takeuchi, T. et al. (1981) A new antitumor antibiotic, spergualin: isolation and antitumor activity. J Antibiot (Tokyo) 34, 1619–1621, PubMed ID: 82141987
79. Hibasami, H. et al. (1991) 15-Deoxyspergualin, an antiproliferative agent for human and mouse leukemia cells shows inhibitory effects on the synthetic pathway of polyamines. Anticancer Res 11, 325–330, PubMed ID: 91206925
80. Ochiai, T. et al. (1987) Prolongation of rat heart allograft survival by 15-deoxyspergualin. J Antibiot (Tokyo) 40, 249–250, PubMed ID: 87194245
81. Takahara, S. et al. (1992) The in vitro immunosuppressive effect of deoxymethylspergualin in man as compared with FK506 and cyclosporine. Transplantation 53, 914–918, PubMed ID: 92229859
82. Kerr, P.G. and Atkins, R.C. (1989) The effects of deoxyspergualin on lymphocytes and monocytes in vivo and in vitro. Transplantation 48, 1048–1052, PubMed ID: 90085322
83. Nishimura, K. and Tokunaga, T. (1988) Mode of action of 15-deoxyspergualin (DSG): Effects on induction and effector function of cytotoxic T lymphocytes (CTL). Int J Immunopharmacol 10 (Suppl. 1), Abstract WS21–2
84. Nadler, S.G. et al. (1998) Identification of a binding site on Hsc70 for the immunosuppressant 15- deoxyspergualin. Biochem Biophys Res Commun 253, 176–180, PubMed ID: 99092399
85. Odaka, C., Toyoda, E. and Nemoto, K. (1998) Immunosuppressant deoxyspergualin induces apoptotic cell death in dividing cells. Immunology 95, 370–376, PubMed ID: 99069296
86. Waaga, A.M. et al. (1990) The immunosuppressive agent 15-deoxyspergualin induces tolerance and modulates MHC-antigen expression and interleukin-1 production in the early phase of rat allograft responses. Transplant Proc 22, 1613–1614, PubMed ID: 90357509
87. Pai, L.H. et al. (1990) Inhibition of antibody response to Pseudomonas exotoxin and an immunotoxin containing Pseudomonas exotoxin by 15-deoxyspergualin in mice. Cancer Res 50, 7750–7753, PubMed ID: 91070529
88. Sterbenz, K.G. and Tepper, M.A. (1993) Effects of 15-deoxyspergualin on the expression of surface immunoglobulin in 70Z/3.12 murine pre-B cell line. Ann N Y Acad Sci 685, 205–206, PubMed ID: 93370851
89. Thomas, F.T. et al. (1993) 15-Deoxyspergualin: a novel immunosuppressive drug with clinical potential. Ann N Y Acad Sci 685, 175–192, PubMed ID: 93370847
90. Williams, P. et al. (1997) Characterization of renal ischemia-reperfusion injury in rats. J Pharmacol Toxicol Methods 37, 1–7, PubMed ID: 97240822
91. Muindi, J.F. et al. (1991) Clinical pharmacology of deoxyspergualin in patients with advanced cancer. Cancer Res 51, 3096–3101, PubMed ID: 91249325
92. Reichenspurner, H. et al. (1990) 15-Deoxyspergualin after cardiac and renal allotransplantation in primates. Transplant Proc 22, 1618–1619, PubMed ID: 90357511
93. Schorlemmer, H.U., Dickneite, G. and Seiler, F.R. (1990) Treatment of acute rejection episodes and induction of tolerance in rat skin allotransplantation by 15-deoxyspergualin.
94. Transplant Proc 22, 1626–1630, PubMed ID: 90357515
95. Amemiya, H. et al. (1989) A new immunosuppressive agent, 15-deoxyspergualin, in dog renal allografting. Transplant Proc 21, 3468–3470, PubMed ID: 89299159
96. Amemiya, H. et al. (1990) A novel rescue drug, 15-deoxyspergualin. First clinical trials for recurrent graft rejection in renal recipients. Transplantation 49, 337–343, PubMed ID: 90162957
97. Amemiya, H. (1993) Deoxyspergualin: clinical trials in renal graft rejection. Japan Collaborative Transplant Study of Deoxyspergualin. Ann N Y Acad Sci 685, 196–201, PubMed ID: 93370849
98. Kyo, M. et al. (1995) Histopathological classification and clinical effects of kidney transplant rejection treated with 15-deoxyspergualin. Transplant Proc 27, 1012–1013, PubMed ID: 95184356
99. Fujita, T. et al. (1994) Fungal metabolites. Part 11. A potent immunosuppressive activity found in Isaria sinclairii metabolite. J Antibiot (Tokyo) 47, 208–215, PubMed ID: 94201101
100. Fujita, T. et al. (1995) Simple compounds, 2-alkyl-2-amino-1,3-propanediols have potent immunosuppressive activity. Bio Med Chem Lett 5, 847–852
101. Wang, M.E. et al. (1998) Immunosuppressive effects of FTY720 alone or in combination with cyclosporine and/or sirolimus. Transplantation 65, 899–905, PubMed ID: 98224764
102. Meno-Tetang, G.M. et al. (2000) Pharmacokinetic/pharmacodynamic modeling of the trafficking effects of FTY720 on rat immune cells. Transplantation 69, S193, Abstract 305
103. Miyake, Y. et al. (1994) FTY720 effect on palmitolyltransferase activity in IL-2 dependent CTLL-2 cell line. Abstracts of the 16th Symposium on the Interaction Between Biological Membranes and Drugs (Kyoto), Abstract 21
104. Suzuki, S. et al. (1996) A novel immunosuppressant, FTY720, with a unique mechanism of action, induces long-term graft acceptance in rat and dog allotransplantation. Transplantation 61, 200–205, PubMed ID: 96166722
105. Chiba, K. et al. (1998) FTY720, a novel immunosuppressant, induces sequestration of circulating mature lymphocytes by acceleration of lymphocyte homing in rats. I. FTY720 selectively decreases the number of circulating mature lymphocytes by acceleration of lymphocyte homing. J Immunol 160, 5037–5044, PubMed ID: 98250135
106. Hoshino, Y. et al. (1995) FTY720, A novel immunosuppressant, possessing unique mechanism. II. Synergistic prolongation of allograft survival in combination with cyclosporin in rat and do. San Francisco: 9th International Congress of Immunology, Abstract 864
107. Troncoso, P. et al. (1999) Prophylaxis of acute renal allograft rejection using FTY720 in combination with subtherapeutic doses of cyclosporine. Transplantation 67, 145–151, PubMed ID: 99118784
108. Crooke, R.M. et al. (1995) In vitro pharmacokinetics of phosphorothioate antisense oligonucleotides. J Pharmacol Exp Ther 275, 462–473, PubMed ID: 96017380
109. Akhtar, S., Kole, R. and Juliano, R.L. (1991) Stability of antisense DNA oligodeoxynucleotide analogs in cellular extracts and sera. Life Sci 49, 1793–1801, PubMed ID: 92048173
110. Hoke, G.D. et al. (1991) Effects of phosphorothioate capping on antisense oligonucleotide stability, hybridization and antiviral efficacy versus herpes simplex virus infection. Nucleic Acids Res 19, 5743–5748, PubMed ID: 92051325
111. Altmann, K.H. et al. (1996) Second-generation antisense oligonucleotides: structure-activity relationships and the design of improved signal-transduction inhibitors. Biochem Soc Trans 24, 630–637, PubMed ID: 97033070
112. Agrawal, S. et al. (1995) Absorption, tissue distribution and in vivo stability in rats of a hybrid antisense oligonucleotide following oral administration. Biochem Pharmacol 50, 571–576, PubMed ID: 95374577
113. Nicklin, P.L. et al. (1998) Pulmonary bioavailability of a phosphorothioate oligonucleotide (CGP 64128A): comparison with other delivery routes. Pharm Res 15, 583–591, PubMed ID: 98249554
114. Cossum, P.A. et al. (1993) Disposition of the 14C-labeled phosphorothioate oligonucleotide ISIS 2105 after intravenous administration to rats. J Pharmacol Exp Ther 267, 1181–1190, PubMed ID: 94087567
115. Glover, J.M. et al. (1997) Phase I safety and pharmacokinetic profile of an intercellular adhesion molecule-1 antisense oligodeoxynucleotide (ISIS 2302). J Pharmacol Exp Ther 282, 1173–1180, PubMed ID: 97461142
116. Levin, A.A. et al. (1988) Toxicity of oligodeoxynucleotide therapeutic agents. In Antisense Research Applications (Crooke, S.T., ed.), pp. 169–216, Springer-Verlag
117. Henry, S.P. et al. (1997) Evaluation of the toxicity of ISIS 2302, a phosphorothioate oligonucleotide, in a four-week study in cynomolgus monkeys. Toxicology 120, 145–155, PubMed ID: 97327534
118. Henry, S.P. et al. (1997) Activation of the alternative pathway of complement by a phosphorothioate oligonucleotide: potential mechanism of action. J Pharmacol Exp Ther 281, 810–816, PubMed ID: 97296920
119. Lappin, J. et al. (1998) A phase I study: the side-effect profile of an intercellular adhesion molecule-1 antisense phosphorothioate oligodeoxynucleotide, ISIS 2302. American Society of Transplant Physicians, Chicago, IL, USA, vol. 139, Abstract 244
120. Stepkowski, S.M. et al. (1994) Blocking of heart allograft rejection by intercellular adhesion molecule-1 antisense oligonucleotides alone or in combination with other immunosuppressive modalities [published erratum appears in J Immunol 1995 Feb 1; 154(3): 1521]. J Immunol 153, 5336–5346, PubMed ID: 95052702
121. Poston, R.S. et al. (1998) Ex vivo gene therapy prevents chronic graft vascular disease in cardiac allografts. J Thorac Cardiovasc Surg 116, 386–396, PubMed ID: 98400505
122. Lisziewicz, J. et al. (1994) Antisense oligodeoxynucleotide phosphorothioate complementary to Gag mRNA blocks replication of human immunodeficiency virus type 1 in human peripheral blood cells. Proc Natl Acad Sci U S A 91, 7942–7946, PubMed ID: 94336663
123. Zhang, H. et al. (1999) Antisense oligonucleotide inhibition of hepatitis C virus (HCV) gene expression in livers of mice infected with an HCV-vaccinia virus recombinant. Antimicrob Agents Chemother 43, 347–353, PubMed ID: 99143904
124. Monia, B.P. et al. (1996) Antitumor activity of a phosphorothioate antisense oligodeoxynucleotide targeted against C-raf kinase. Nat Med 2, 668–675, PubMed ID: 96233648
125. Yacyshyn, B.R. et al. (1998) A placebo-controlled trial of ICAM-1 antisense oligonucleotide in the treatment of Crohn's disease. Gastroenterology 114, 1133–1142, PubMed ID: 98282350
126. Stepkowski, S.M. et al. (1998) Protection against allograft rejection with intercellular adhesion molecule-1 antisense oligodeoxynucleotides. Transplantation 66, 699–707, PubMed ID: 98442775
127. Isobe, M. et al. (1997) Regulation by differential development of Th1 and Th2 cells in peripheral tolerance to cardiac allograft induced by blocking ICAM- 1/LFA-1 adhesion. Circulation 96, 2247–2253, PubMed ID: 97477134
128. Moriyama, H. et al. (1996) Induction of tolerance in murine autoimmune diabetes by transient blockade of leukocyte function-associated antigen-1/intercellular adhesion molecule-1 pathway. J Immunol 157, 3737–3743, PubMed ID: 97025487
129. Katz, S.M. et al. (1997) Effect of ICAM-1/LFA-1 blockade on pancreatic islet allograft survival, function, and early cytokine production. Transplant Proc 29, 748–749, PubMed ID: 97232560
130. Tilney, N.L. and Guttmann, R.D. (1997) Effects of initial ischemia/reperfusion injury on the transplanted kidney. Transplantation 64, 945–947, PubMed ID: 98018658
131. Bonventre, J.V. (1993) Mechanisms of ischemic acute renal failure. Kidney Int 43, 1160–1178, PubMed ID: 93287582
132. Rabb, H. et al. (1995) Antibodies to ICAM-1 protect kidneys in severe ischemic reperfusion injury. Biochem Biophys Res Commun 211, 67–73, PubMed ID: 95298051
133. Hammond, E.H. et al. (1990) Relationship of OKT3 sensitization and vascular rejection in cardiac transplant patients receiving OKT3 rejection prophylaxis. Transplantation 50, 776–782, PubMed ID: 91048816
134. Haller, H. et al. (1996) Antisense oligonucleotides for ICAM-1 attenuate reperfusion injury and renal failure in the rat. Kidney Int 50, 473–480, PubMed ID: 96437628
135. Bennett, C.F. et al. (1996) Pharmacokinetics in mice of a [3H]-labeled phophorothioate oligonucleotide formulated in the presence and absence of a cathionic lipid. J Controll Rel 41, 121–130
136. Chen, W. et al. (1999) Perfusion of kidneys with unformulated “naked” intercellular adhesion molecule-1 antisense oligodeoxynucleotides prevents ischemic/reperfusion injury. Transplantation 68, 880–887, PubMed ID: 99443413
137. Noiri, E. et al. (1996) In vivo targeting of inducible NO synthase with oligodeoxynucleotides protects rat kidney against ischemia. J Clin Invest 97, 2377–2383, PubMed ID: 96217602
138. Shimamura, T. et al. (1999) Protective role of nitric oxide in ischemia and reperfusion injury of the liver. J Am Coll Surg 188, 43–52, PubMed ID: 99112447
139. Shah, K.A., Shurey, S. and Green, C.J. (1997) Apoptosis after intestinal ischemia-reperfusion injury: a morphological study. Transplantation 64, 1393–1397, PubMed ID: 98052193