Ex vivo alloanergization with belatacept: A strategy to selectively modulate alloresponses after transplantation

Cell Transplantation

Volumn 21, Issue 9, 2012, Pages 2047-2061

  Davies, Jeff K ^a,b,c   Barbon, Christine M ^a   Voskertchian, Annie ^a   Nadler, Lee M ^a,b   Guinan, Eva C ^d  

^a DANA FARBER CANCER INSTITUTE   (United States)

^b BRIGHAM AND WOMEN S HOSPITAL   (United States)

^c QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

^d HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Alloreactivity; Anergization; Belatacept; Costimulatory blockade; Regulatory T cells; Transplantation

Indexed keywords

ABATACEPT; ALLOANTIGEN; B7 ANTIGEN; BELATACEPT; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4 IMMUNOGLOBULIN; IMMUNOGLOBULIN; UNCLASSIFIED DRUG;

ARTICLE; CELL EXPANSION; CELL MIGRATION; CELL POPULATION; CELL PROLIFERATION; CONTROLLED STUDY; EPSTEIN BARR VIRUS; EX VIVO STUDY; GRAFT RECIPIENT; GRAFT REJECTION; HLA TYPING; HUMAN; HUMAN CELL; IMMUNITY; IMMUNOREGULATION; ORGAN TRANSPLANTATION; PERIPHERAL BLOOD MONONUCLEAR CELL; PRIORITY JOURNAL;

EPITOPES; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HLA ANTIGENS; HUMANS; IMMUNOCONJUGATES; IMMUNOSUPPRESSIVE AGENTS; ISOANTIGENS; LEUKOCYTES, MONONUCLEAR; T-LYMPHOCYTES, REGULATORY; TRANSPLANTATION IMMUNOLOGY;

HUMAN HERPESVIRUS 4;

EID: 84869758998     PISSN: 09636897     EISSN: None     Source Type: Journal    
DOI: 10.3727/096368912X637479     Document Type: Article

References (52)

1. Abrams, J. R.; Lebwohl, M. G.; Guzzo, C. A.; 1. Jegasothy, B. V.; Goldfarb, M. T.; Goffe, B. S.; Menter, A.; Lowe, N. J.; Krueger, G.; Brown, M. J.; Weiner, R. S.; Birkhofer, M. J.; Warner, G. L.; Berry, K. K.; Linsley, P. S.; Krueger, J. G.; Ochs, H. D.; Kelley, S. L.; Kang, S. CTLA4Igmediated blockade of T-cell costimulation in patients with psoriasis vulgaris. J. Clin. Invest. 103(9):1243-1252; 1999.
2. Bluestone, J. A.; Liu, W.; Yabu, J. M.; Laszik, Z. G.; Putnam, A.; Belingheri, M.; Gross, D. M.; Townsend, R. M.; Vincenti, F. The effect of costimulatory and interleukin
3. Canadian Multicentre Transplant Study Group. A randomized clinical trial of cyclosporine in cadaveric renal transplantation. Analysis at three years. N. Engl. J. Med. 314(19):1219-1225; 1986.
4. Chavez, H.; Beaudreuil, S.; Abbed, K.; Taoufic, Y.; Kriaa, F.; Charpentier, B.; Durrbach, A. Absence of CD4CD25 regulatory T cell expansion in renal transplanted patients treated in vivo with Belatacept mediated CD28-CD80/86 blockade. Transpl. Immunol. 17(4):243-248; 2007.
5. Danesi, R.; Del Tacca, M. Hematologic toxicity of immunosuppressive treatment. Transplant. Proc. 36(3):703-704; 2004.
6. Darenkov, I. A.; Marcarelli, M. A.; Basadonna, G. P.; Friedman, A. L.; Lorber, K. M.; Howe, J. G.; Crouch, J.; Bia, M. J.; Kliger, A. S.; Lorber, M. I. Reduced incidence of Epstein-Barr virus-associated posttransplant lymphoproliferative disorder using preemptive antiviral therapy. Transplantation 64(6):848-852; 1997.
7. Davies, J. K.; Gribben, J. G.; Brennan, L. L.; Yuk, D.; Nadler, L. M.; Guinan, E. C. Outcome of alloanergized haploidentical bone marrow transplantation after ex vivo costimulatory blockade: Results of 2 phase 1 studies. Blood 112(6):2232-2241; 2008.
8. Davies, J. K.; Nadler, L. M.; Guinan, E. C. Expansion of allospecific regulatory T cells after anergized, mismatched bone marrow transplantation. Sci. Transl. Med. 1(1):1ra3; 2009.
9. Davies, J. K.; Singh, H.; Huls, H.; Yuk, D.; Lee, D. A.; Kebriaei, P.; Champlin, R. E.; Nadler, L. M.; Guinan, E. C.; Cooper, L. J. Combining CD19 redirection and alloanergization to generate tumor-specific human T cells for allogeneic cell therapy of B-cell malignancies. Cancer Res. 70(10):3915-3924; 2010.
10. Davies, J. K.; Yuk, D.; Nadler, L. M.; Guinan, E. C. Induction of alloanergy in human donor T cells without loss of pathogen or tumor immunity. Transplantation 86(6):854-864; 2008.
11. Durrbach, A.; Pestana, J. M.; Pearson, T.; Vincenti, F.; Garcia, V. D.; Campistol, J.; Rial Mdel, C.; Florman, S.; Block, A.; Di Russo, G.; Xing, J.; Garg, P.; Grinyo, J. A phase III study of belatacept versus cyclosporine in kidney transplants from extended criteria donors (BENEFIT-EXT study). Am. J. Transplant. 10(3):547-557; 2010.
12. Gimmi, C. D.; Freeman, G. J.; Gribben, J. G.; Gray, G.; Nadler, L. M. Human T-cell clonal anergy is induced by antigen presentation in the absence of B7 costimulation. Proc. Natl. Acad. Sci. USA 90(14):6586-6590; 1993.
13. Godfrey, W. R.; Ge, Y. G.; Spoden, D. J.; Levine, B. L.; June, C. H.; Blazar, B. R.; Porter, S. B. In vitro-expanded human CD4(+)CD25(+) T-regulatory cells can markedly inhibit allogeneic dendritic cell-stimulated MLR cultures. Blood 104(2):453-461; 2004.
14. Gottschalk, S.; Rooney, C. M.; Heslop, H. E. Post-transplant lymphoproliferative disorders. Annu. Rev. Med. 56:29-44; 2005.
15. Greenfield, E. A.; Nguyen, K. A.; Kuchroo, V. K. CD28/B7 costimulation: A review. Crit. Rev. Immunol. 18(5):389-418; 1998.
16. Gribben, J. G.; Guinan, E. C.; Boussiotis, V. A.; Ke, X. Y.; Linsley, L.; Sieff, C.; Gray, G. S.; Freeman, G. J.; Nadler, L. M. Complete blockade of B7 family-mediated costimulation is necessary to induce human alloantigenspecific anergy: A method to ameliorate graft-versus-host disease and extend the donor pool. Blood 87(11):4887-4893; 1996.
17. Guinan, E. C.; Boussiotis, V. A.; Neuberg, D.; Brennan, L. L.; Hirano, N.; Nadler, L. M.; Gribben, J. G. Transplantation of anergic histoincompatible bone marrow allografts. N. Engl. J. Med. 340(22):1704-1714; 1999.
18. Haining, W. N.; Davies, J.; Kanzler, H.; Drury, L.; Brenn, T.; Evans, J.; Angelosanto, J.; Rivoli, S.; Russell, K.; George, S.; Sims, P.; Neuberg, D.; Li, X.; Kutok, J.; Morgan, J.; Wen, P.; Demetri, G.; Coffman, R. L.; Nadler, L. M. CpG oligodeoxynucleotides alter lymphocyte and dendritic cell trafficking in humans. Clin. Cancer Res. 14(17):5626-5634; 2008.
19. Kitazawa, Y.; Fujino, M.; Li, X. K.; Xie, L.; Ichimaru, N.; Okumi, M.; Nonomura, N.; Tsujimura, A.; Isaka, Y.; Kimura, H.; Hunig, T.; Takahara, S. Superagonist CD28 antibody preferentially expanded Foxp3-expressing nTreg cells and prevented graft-versus-host diseases. Cell Transplant. 18(5):627-637; 2009.
20. Kitazawa, Y.; Li, X. K.; Liu, Z.; Kimura, H.; Isaka, Y.; Hunig, T.; Takahara, S. Prevention of graft-versus-host diseases by in vivo supCD28mAb-expanded antigen-specific nTreg cells. Cell Transplant. 19(6):765-774; 2010.
21. Koenen, H. J.; Joosten, I. Blockade of CD86 and CD40 induces alloantigen-specific immunoregulatory T cells that remain anergic even after reversal of hyporesponsiveness. Blood 95(10):3153-3161; 2000.
22. Kremer, J. M.; Westhovens, R.; Leon, M.; Di Giorgio, E.; Alten, R.; Steinfeld, S.; Russell, A.; Dougados, M.; Emery, P.; Nuamah, I. F.; Williams, G. R.; Becker, J. C.; Hagerty, D. T.; Moreland, L. W. Treatment of rheumatoid arthritis by selective inhibition of T-cell activation with fusion protein CTLA4Ig. N. Engl. J. Med. 349(20):1907-1915; 2003.
23. Lacerda, J. F.; Ladanyi, M.; Louie, D. C.; Fernandez, J. M.; Papadopoulos, E. B.; O'Reilly, R. J. Human Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes home preferentially to and induce selective regressions of autologous EBV-induced B cell lymphoproliferations in xenografted C. B-17 scid/scid mice. J. Exp. Med. 183(3):1215-1228; 1996.
24. Lacerda, J. F.; O'Reilly, R. J. Characteristics of human EBV-specific cytotoxic T lymphocytes utilized for adoptive immunotherapy of EBV-induced lymphoproliferations in xenografted SCID mice. Ann. Oncol. 8 Suppl 2:137-140; 1997.
25. Larsen, C. P.; Pearson, T. C.; Adams, A. B.; Tso, P.; Shirasugi, N.; Strobert, E.; Anderson, D.; Cowan, S.; Price, K.; Naemura, J.; Emswiler, J.; Greene, J.; Turk, L. A.; Bajorath, J.; Townsend, R.; Hagerty, D.; Linsley, P. S.; Peach, R. J. Rational development of LEA29Y (belatacept), a high-affinity variant of CTLA4-Ig with potent immunosuppressive properties. Am. J. Transplant. 5(3):443-453; 2005.
26. Lenschow, D. J.; Zeng, Y.; Thistlethwaite, J. R.; Montag, A.; Brady, W.; Gibson, M. G.; Linsley, P. S.; Bluestone, J. A. Long-term survival of xenogeneic pancreatic islet grafts induced by CTLA4lg. Science 257(5071):789-792; 1992.
27. Linsley, P. S.; Brady, W.; Urnes, M.; Grosmaire, L. S.; Damle, N. K.; Ledbetter, J. A. CTLA-4 is a second receptor for the B cell activation antigen B7. J. Exp. Med. 174(3):561-569; 1991.
28. Linsley, P. S.; Wallace, P. M.; Johnson, J.; Gibson, M. G.; Greene, J. L.; Ledbetter, J. A.; Singh, C.; Tepper, M. A. Immunosuppression in vivo by a soluble form of the CTLA-4 T cell activation molecule. Science 257(5071):792-795; 1992.
29. + T reg cells. J. Exp. Med. 203(7):1701-1711; 2006.
30. Luo, Z.; Gotoh, M.; Grochowiecki, T.; Tanaka, T.; Kimura, F.; Kawashima, H.; Yagita, H.; Okumura, K.; Miyasaka, M. Anergic T cells generated in vitro suppress rejection response to islet allografts. Transplantation 69(10):2144-2148; 2000.
31. Marelli-Berg, F. M.; Cannella, L.; Dazzi, F.; Mirenda, V. The highway code of T cell trafficking. J. Pathol. 214(2):179-189; 2008.
32. + T lymphocytes after partially T-depleted allogeneic stem cell transplantation may identify patients at very high risk for progressive EBV reactivation and lymphoproliferative disease. Blood 101(11):4290-4297; 2003.
33. Miller, L. W. Cardiovascular toxicities of immunosuppressive agents. Am. J. Transplant. 2(9):807-818; 2002.
34. Miura, Y.; Thoburn, C. J.; Bright, E. C.; Phelps, M. L.; Shin, T.; Matsui, E. C.; Matsui, W. H.; Arai, S.; Fuchs, E. J.; Vogelsang, G. B.; Jones, R. J.; Hess, A. D. Association of Foxp3 regulatory gene expression with graft-versus-host disease. Blood 104(7):2187-2193; 2004.
35. Murray, J. E.; Merrill, J. P.; Harrison, J. H.; Wilson, R. E.; Dammin, G. J. Prolonged survival of human-kidney homografts by immunosuppressive drug therapy. N. Engl. J. Med. 268:1315-1323; 1963.
36. Muthukumar, T.; Dadhania, D.; Ding, R.; Snopkowski, C.; Naqvi, R.; Lee, J. B.; Hartono, C.; Li, B.; Sharma, V. K.; Seshan, S. V.; Kapur, S.; Hancock, W. W.; Schwartz, J. E.; Suthanthiran, M. Messenger RNA for FOXP3 in the urine of renal-allograft recipients. N. Engl. J. Med. 353(22):2342-2351; 2005.
37. Nankivell, B. J.; Alexander, S. I. Rejection of the kidney allograft. N. Engl. J. Med. 363(15):1451-1462; 2010.
38. Norman, D. J.; Chatenoud, L.; Cohen, D.; Goldman, M.; Shield, C. F., 3rd. Consensus statement regarding OKT3-induced cytokine-release syndrome and human antimouse antibodies. Transplant Proc. 25(2 Suppl 1):89-92; 1993.
39. Ortho Multicenter Transplant Study Group. A randomized clinical trial of OKT3 monoclonal antibody for acute rejection of cadaveric renal transplants. N. Engl. J. Med. 313(6):337-342; 1985.
40. Perkins, D.; Wang, Z.; Donovan, C.; He, H.; Mark, D.; Guan, G.; Wang, Y.; Walunas, T.; Bluestone, J.; Listman, J.; Finn, P. W. Regulation of CTLA-4 expression during T cell activation. J. Immunol. 156(11):4154-4159; 1996.
41. Posselt, A. M.; Szot, G. L.; Frassetto, L. A.; Masharani, U.; Tavakol, M.; Amin, R.; McElroy, J.; Ramos, M. D.; Kerlan, R. K.; Fong, L.; Vincenti, F.; Bluestone, J. A.; Stock, P. G. Islet transplantation in type 1 diabetic patients using calcineurin inhibitor-free immunosuppressive protocols based on T-cell adhesion or costimulation blockade. Transplantation 90(12):1595-1601; 2010.
42. Rezvani, K.; Mielke, S.; Ahmadzadeh, M.; Kilical, Y.; Savani, B. N.; Zeilah, J.; Keyvanfar, K.; Montero, A.; Hensel, N.; Kurlander, R.; Barrett, A. J. High donor FOXP3-positive regulatory T-cell (Treg) content is associated with a low risk of GVHD following HLA-matched allogeneic SCT. Blood 108(4):1291-1297; 2006.
43. Stegall, M. D.; Raghavaiah, S.; Gloor, J. M. The (re)emergence of B cells in organ transplantation. Curr. Opin. Organ Transplant. 15(4):451-455; 2010.
44. Tan, P.; Anasetti, C.; Hansen, J. A.; Melrose, J.; Brunvand, M.; Bradshaw, J.; Ledbetter, J. A.; Linsley, P. S. Induction of alloantigen-specific hyporesponsiveness in human T lymphocytes by blocking interaction of CD28 with its natural ligand B7/BB1. J. Exp. Med. 177(1):165-173; 1993.
45. Taylor, P. A.; Friedman, T. M.; Korngold, R.; Noelle, R. J.; Blazar, B. R. Tolerance induction of alloreactive T cells via ex vivo blockade of the CD40:CD40L costimulatory pathway results in the generation of a potent immune regulatory cell. Blood 99(12):4601-4609; 2002.
46. Taylor, P. A.; Lees, C. J.; Blazar, B. R. The infusion of ex vivo activated and expanded CD4(+)CD25(+) immune regulatory cells inhibits graft-versus-host disease lethality. Blood 99(10):3493-3499; 2002.
47. van Baarle, D.; Hovenkamp, E.; Callan, M. F.; Wolthers, K. C.; Kostense, S.; Tan, L. C.; Niesters, H. G.; Osterhaus, A. D.; McMichael, A. J.; van Oers, M. H.; Miedema, F. Dysfunctional Epstein-Barr virus (EBV)-specific CD8(+) T lymphocytes and increased EBV load in HIV-1 infected individuals progressing to AIDS-related non-Hodgkin lymphoma. Blood 98(1):146-155; 2001.
48. Vermeiren, J.; Ceuppens, J. L.; Haegel-Kronenberger, H.; De Boer, M.; Boon, L.; Van Gool, S. W. Blocking B7 and CD40 co-stimulatory molecules decreases antiviral T cell activity. Clin. Exp. Immunol. 135(2):253-258; 2004.
49. Vincenti, F.; Blancho, G.; Durrbach, A.; Friend, P.; Grinyo, J.; Halloran, P. F.; Klempnauer, J.; Lang, P.; Larsen, C. P.; Muhlbacher, F.; Nashan, B.; Soulillou, J. P.; Vanrenterghem, Y.; Wekerle, T.; Agarwal, M.; Gujrathi, S.; Shen, J.; Shi, R.; Townsend, R.; Charpentier, B. Five-year safety and efficacy of belatacept in renal transplantation. J. Am. Soc. Nephrol. 21(9):1587-1596; 2010.
50. Vincenti, F.; Charpentier, B.; Vanrenterghem, Y.; Rostaing, L.; Bresnahan, B.; Darji, P.; Massari, P.; Mondragon-Ramirez, G. A.; Agarwal, M.; Di Russo, G.; Lin, C. S.; Garg, P.; Larsen, C. P. A phase III study of belatacept-based immunosuppression regimens versus cyclosporine in renal transplant recipients (BENEFIT study). Am. J. Transplant. 10(3):535-546; 2010.
51. Vincenti, F.; Larsen, C.; Durrbach, A.; Wekerle, T.; Nashan, B.; Blancho, G.; Lang, P.; Grinyo, J.; Halloran, P. F.; Solez, K.; Hagerty, D.; Levy, E.; Zhou, W.; Natarajan, K.; Charpentier, B. Costimulation blockade with belatacept in renal transplantation. N. Engl. J. Med. 353(8):770-781; 2005.
52. + T cells of allograft rejection mice. Cell Transplant. 20(2):333-350; 2011.