Profile of belatacept and its potential role in prevention of graft rejection following renal transplantation

Drug Design, Development and Therapy

Volumn 4, Issue , 2010, Pages 375-382

  Gupta, Gaurav ^a   Womer, Karl L ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Graft rejection; Immunosuppression; Kidney transplantation; Post transplant lymphoproliferative disease; T cell costimulation

Indexed keywords

BASILIXIMAB; BELATACEPT; CALCINEURIN INHIBITOR; CD86 ANTIGEN; CYCLOSPORIN; IMMUNOSUPPRESSIVE AGENT; MAJOR HISTOCOMPATIBILITY ANTIGEN; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; RAPAMYCIN; STEROID; T LYMPHOCYTE RECEPTOR; TACROLIMUS; ABATACEPT; ANTIBODY CONJUGATE;

ACUTE GRAFT REJECTION; ALLOIMMUNITY; ANTIGEN PRESENTING CELL; CARDIOVASCULAR DISEASE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL PROLIFERATION; CENTRAL NERVOUS SYSTEM DISEASE; COMBINATION CHEMOTHERAPY; DRUG BLOOD LEVEL; DRUG DOSE REGIMEN; DRUG MECHANISM; DRUG SAFETY; DRUG TOLERABILITY; GLOMERULUS FILTRATION RATE; GRAFT SURVIVAL; HERPES VIRUS INFECTION; HUMAN; IMMUNE RESPONSE; KIDNEY GRAFT REJECTION; KIDNEY TRANSPLANTATION; LYMPHOPROLIFERATIVE DISEASE; MAINTENANCE THERAPY; MONOTHERAPY; NONHUMAN; PNEUMOCYSTIS PNEUMONIA; POLYOMAVIRUS INFECTION; REVIEW; SIGNAL TRANSDUCTION; T LYMPHOCYTE ACTIVATION; THROMBOTIC THROMBOCYTOPENIC PURPURA; ANIMAL; DRUG EFFECT; GRAFT REJECTION; METABOLISM; METHODOLOGY; T LYMPHOCYTE;

ANIMALS; GRAFT REJECTION; GRAFT SURVIVAL; HUMANS; IMMUNOCONJUGATES; IMMUNOSUPPRESSIVE AGENTS; KIDNEY TRANSPLANTATION; T-LYMPHOCYTES;

EID: 79952476108     PISSN: 11778881     EISSN: None     Source Type: Journal    
DOI: 10.2147/DDDT.S10432     Document Type: Review

References (53)

1. Suthanthiran M, Strom TB. Renal transplantation. N Engl J Med. 1994; 331(6):365-376.
2. Organ Procurement and Transplant Network/Scientific Registry of Transplant Recipients Annual Report. 2009 Donation and transplantation trends. Available at: http://optn.transplant.hrsa.gov/latestData. Accessed 2010 Nov 10.
3. Cecka JM. The OPTN/UNOS Renal Transplant Registry. Clin Transpl. 2005:1-16.
4. Samaniego M, Becker BN, Djamali A. Drug insight: Maintenance immunosuppression in kidney transplant recipients. Nat Clin Pract Nephrol. 2006;2(12):688-699.
5. Tantravahi J, Womer KL, Kaplan B. Why hasn't eliminating acute rejection improved graft survival? Annu Rev Med. 2007;58:369-385.
6. Organ Procurement and Transplantation Network, based on OPTN data as of September 24, 2010. Available at: http://optn.transplant.hrsa.gov/latestData. Accessed 2010 Nov 10.
7. Pascual M, Theruvath T, Kawai T, Tolkoff-Rubin N, Cosimi AB. Strategies to improve long-term outcomes after renal transplantation. N Engl J Med. 2002;346(8):580-590.
8. Nankivell BJ, Borrows RJ, Fung CL, O'Connell PJ, Allen RD, Chapman JR. The natural history of chronic allograft nephropathy. N Engl J Med. 2003;349(24):2326-2333.
9. Arend SM, Mallat MJ, Westendorp RJ, van der Woude FJ, van Es LA. Patient survival after renal transplantation; more than 25 years follow-up. Nephrol Dial Transplant. 1997;12(8):1672-1679.
10. Ojo AO. Cardiovascular complications after renal transplantation and their prevention. Transplantation. 2006;82(5):603-611.
11. Womer K, Rabb H. Immunosuppressive medications in kidney transplantation. In: Feehally J, Johnson R, Floege J, editors. Comprehensive Clinical Nephrology. 4th ed. Mosby; 2010.
12. Glotz D, Charpentier B, Abramovicz D, et al. Thymoglobulin induction and sirolimus versus tacrolimus in kidney transplant recipients receiving mycophenolate mofetil and steroids. Transplantation. 2010;89(12):1511-1517.
13. Jacquet A, Francois H, Frangie C, Ahmad L, Charpentier B, Durrbach A. Prevention of calcineurin inhibitor nephrotoxicity in renal transplantation. Transpl Immunol. 2008;20(1-2):29-31.
14. Buchler M, Caillard S, Barbier S, et al. Sirolimus versus cyclosporine in kidney recipients receiving thymoglobulin, mycophenolate mofetil and a 6-month course of steroids. Am J Transplant. 2007;7(11):2522-2531.
15. 2008 Annual Report of the US Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients: Transplant Data 1998-2007. Available at: http://www.ustransplant.org/annual_reports/current/506d_ki.htm. Accessed 2010 Nov 10.
16. Cooper JE, Wiseman AC. Novel immunosuppressive agents in kidney transplantation. Clin Nephrol. 2010;73(5):333-343.
17. Huang E, Womer K, Vincenti F. Biological agents in kidney transplantation. In: Pereira B, Sayegh M, Blake P, editors. Chronic Kidney Disease, Dialysis, and Transplantation. 3rd ed. Philadelphia, PA: Elsevier Saunders; 2010.
18. Womer K, Rabb H. Immunologic principles in kidney transplantation. In: Feehally J, Johnson R, Floege J, editors. Comprehensive Clinical Nephrology. 4th ed. Mosby; 2010.
19. Fife BT, Bluestone JA. Control of peripheral T-cell tolerance and autoimmunity via the CTLA-4 and PD-1 pathways. Immunol Rev. 2008;224:166-182.
20. Li XC, Rothstein DM, Sayegh MH. Costimulatory pathways in transplantation: Challenges and new developments. Immunol Rev. 2009; 229(1):271-293.
21. Linsley PS, Wallace PM, Johnson J, et al. Immunosuppression in vivo by a soluble form of the CTLA-4 T cell activation molecule. Science. 1992;257(5071):792-795.
22. Kremer JM, Westhovens R, Leon M, et al. Treatment of rheumatoid arthritis by selective inhibition of T-cell activation with fusion protein CTLA4Ig. N Engl J Med. 2003;349(20):1907-1915.
23. Abrams JR, Kelley SL, Hayes E, et al. Blockade of T lymphocyte costimulation with cytotoxic T lymphocyte-associated antigen 4-immunoglobulin (CTLA4Ig) reverses the cellular pathology of psoriatic plaques, including the activation of keratinocytes, dendritic cells, and endothelial cells. J Exp Med. 2000;192(5):681-694.
24. Levisetti MG, Padrid PA, Szot GL, et al. Immunosuppressive effects of human CTLA4Ig in a non-human primate model of allogeneic pancreatic islet transplantation. J Immunol. 1997;159(11):5187-5191.
25. Linsley PS, Greene JL, Brady W, Bajorath J, Ledbetter JA, Peach R. Human B7-1 (CD80) and B7-2 (CD86) bind with similar avidities but distinct kinetics to CD28 and CTLA-4 receptors. Immunity. 1994;1(9):793-801.
26. Larsen CP, Pearson TC, Adams AB, et al. Rational development of LEA29Y (belatacept), a high-affinity variant of CTLA4-Ig with potent immunosuppressive properties. Am J Transplant. 2005;5(3):443-453.
27. Latek R, Fleener C, Lamian V, et al. Assessment of belatacept-mediated costimulation blockade through evaluation of CD80/86-receptor saturation. Transplantation. 2009;87(6):926-933.
28. Davis PM, Nadler S, Suchard SJ. Belatacept does not mediate complement-dependent cytotoxicity or antibody-dependent cellular cytotoxicity. Am J Transplant. 2008;8:619.
29. Sakaguchi S, Sakaguchi N, Shimizu J, et al. Immunologic tolerance maintained by CD25+ CD4+ regulatory T cells: Their common role in controlling autoimmunity, tumor immunity, and transplantation tolerance. Immunol Rev. 2001;182:18-32.
30. Tang Q, Henriksen KJ, Boden EK, et al. Cutting edge: CD28 controls peripheral homeostasis of CD4+ CD25+ regulatory T cells. J Immunol. 2003;171(7):3348-3352.
31. Rangel EB. Belatacept in clinical and experimental transplantation - progress and promise. Drugs Today (Barc). 2010;46(4):235-242.
32. Bluestone JA, Liu W, Yabu JM, et al. The effect of costimulatory and interleukin 2 receptor blockade on regulatory T cells in renal transplantation. Am J Transplant. 2008;8(10):2086-2096.
33. Vierboom MP, Ossevoort M, Sick EA, Haanstra K, Jonker M. Induction of allograft tolerance through costimulatory blockade: First selection of drugs in vitro. Transpl Immunol. 2003;11(2):215-222.
34. Kirk AD, Tadaki DK, Celniker A, et al. Induction therapy with monoclonal antibodies specific for CD80 and CD86 delays the onset of acute renal allograft rejection in non-human primates. Transplantation. 2001;72(3):377-384.
35. Montgomery SP, Xu H, Tadaki DK, et al. Combination induction therapy with monoclonal antibodies specific for CD80, CD86, and CD154 in nonhuman primate renal transplantation. Transplantation. 2002;74(10):1365-1369.
36. Emamaullee JA, Merani S, Larsen CP, Shapiro AM. Belatacept and basiliximab diminish human antiporcine xenoreactivity and synergize to inhibit alloimmunity. Transplantation. 2008;85(1):118-124.
37. Li C, Yang CW. The pathogenesis and treatment of chronic allograft nephropathy. Nat Rev Nephrol. 2009;5(9):513-519.
38. Vincenti F, Larsen C, Durrbach A, et al. Costimulation blockade with belatacept in renal transplantation. N Engl J Med. 2005;353(8): 770-781.
39. Ferguson R, Vincenti F, Kaufman D, et al. Immunosuppression with belatacept-based, CNI-avoiding and steroid-avoiding regimens vs a tacrolimus-based, steroid-avoid regimen in kidney transplant patients: Results of a 1-year, randomized study. Transplantation. 2010;90 Suppl:156.
40. Vincenti F, Charpentier B, Vanrenterghem Y, et al. A phase III study of belatacept-based immunosuppression regimens versus cyclosporine in renal transplant recipients (BENEFIT study). Am J Transplant. 2008; 10(3):535-546.
41. Larsen C, Grinyo JM, Charpentier B, et al. Belatacept vs cyclosporine in kidney transplant recipients: Two-year outcomes from the BENEFIT study. Transplantation. 2010;90 Suppl. 158
42. Durrbach A, Pestana JM, Pearson T, et al. A phase III study of belatacept versus cyclosporine in kidney transplants from extended criteria donors (BENEFIT-EXT study). Am J Transplant. 2010;10(3):547-557.
43. Durrbach A, Larsen C, Pestana JOM, et al. Belatacept vs cyclosporine in ECD kidney transplants: Two-year outcomes from the BENEFIT-EXT study. Transplantation. 2010;90 Suppl:157.
44. Rostaing L, Nainan G, Rial MC, et al. Switch from a CNI- to a belatacept-based immunosuppressive regimen in kidney transplant recipients is safe and results in better renal function: 12 month results from a Phase II study. Transplantation. 2010;90 Suppl:157.
45. Goring S, Eyawo O, Mills EJ, et al. A mixed treatment comparison of efficacy and cardiometabolic safety of belatacept, cyclospoorine and tacrolimus for immunosuppression therapy in adult renal transplant receipients. Transplantation. 2010;90 Suppl:75.
46. Vincenti F, Kirk AD. What's next in the pipeline. Am J Transplant. 2008;8(10):1972-1981.
47. Ashman N, Chapagain A, Dobbie H, et al. Belatacept as maintenance immunosuppression for postrenal transplant de novo drug-induced thrombotic microangiopathy. Am J Transplant. 2009;9(2): 424-427.
48. Grinyo J, Charpentier B, Pestana J, et al. Safety profile of belatacept in kidney transplant recipients from a pooled analysis of phase II and phase III studies. Transplantation 2010;90 Suppl:156.
49. Vincenti F, Blancho G, Durrbach A, et al. Five-year safety and efficacy of belatacept in renal transplantation. J Am Soc Nephrol. 2010;21(9): 1587-1596.
50. Haidinger M, Hecking M, Memarsadeghi M, et al. Late onset Pneumocystis pneumonia in renal transplantation after long-term immunosuppression with belatacept. Transpl Infect Dis. 2009;11(2): 171-174.
51. Adams AB, Shirasugi N, Jones TR, et al. Development of a chimeric anti-CD40 monoclonal antibody that synergizes with LEA29Y to prolong islet allograft survival. J Immunol. 2005;174(1):542-550.
52. Cardona K, Korbutt GS, Milas Z, et al. Long-term survival of neonatal porcine islets in nonhuman primates by targeting costimulation pathways. Nat Med. 2006;12(3):304-306.
53. Cardona K, Milas Z, Strobert E, et al. Engraftment of adult porcine islet xenografts in diabetic nonhuman primates through targeting of costimulation pathways. Am J Transplant. 2007;7(10):2260-2268.