IL-2-targeted therapy ameliorates the severity of graft-versus-host disease: Ex vivo selective depletion of host-reactive T cells and in vivo therapy

Biology of Blood and Marrow Transplantation

Volumn 18, Issue 4, 2012, Pages 523-535

  Yarkoni, Shai ^a   Prigozhina, Tatyana B ^b   Slavin, Shimon ^c   Askenasy, Nadir ^d  

^a GASR Biotechnology   (Israel)

^b HADASSAH HEBREW UNIVERSITY MEDICAL CENTER   (Israel)

^c International Center for Cell Therapy and Cancer Immunotherapy   (Israel)

^d SCHNEIDER CHILDREN S MEDICAL CENTER OF ISRAEL   (Israel)

Author keywords

Apoptosis; Bone marrow transplantation; Caspase 3; Fusion protein; Interleukin 2; Regulatory T cell

Indexed keywords

CASPASE 3; INTERLEUKIN 2; LIPOPOLYSACCHARIDE; TRANSCRIPTION FACTOR FOXP3; WINGED HELIX TRANSCRIPTION FACTOR;

ALLOIMMUNIZATION; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIGEN EXPRESSION; APOPTOSIS; ARTICLE; CD25+ T LYMPHOCYTE; CD4+ CD25+ T LYMPHOCYTE; CELL PROLIFERATION; CONTROLLED STUDY; DISEASE SEVERITY; EFFECTOR CELL; GRAFT VERSUS HOST REACTION; LYMPH NODE; LYMPHOCYTE; MEMORY T LYMPHOCYTE; MOUSE; NONHUMAN; OUTCOME ASSESSMENT; REGULATORY T LYMPHOCYTE; SPLEEN CELL; SURVIVAL; T CELL DEPLETION; T LYMPHOCYTE;

ADOPTIVE TRANSFER; ANIMALS; ANTIGENS, CD; APOPTOSIS; BONE MARROW TRANSPLANTATION; CASPASE 3; CELLS, CULTURED; GRAFT VS HOST DISEASE; INTERLEUKIN-2; LYMPHOCYTE DEPLETION; MICE; MICE, INBRED STRAINS; MOLECULAR TARGETED THERAPY; RECOMBINANT FUSION PROTEINS; SEVERITY OF ILLNESS INDEX; SPLEEN; T-LYMPHOCYTES; T-LYMPHOCYTES, REGULATORY; TRANSPLANTATION, ISOGENEIC; WHOLE-BODY IRRADIATION;

EID: 84858072808     PISSN: 10838791     EISSN: 15236536     Source Type: Journal    
DOI: 10.1016/j.bbmt.2011.11.016     Document Type: Article

References (79)

1. Shlomchik W.D. Graft-versus-host disease. Nat Rev Immunol 2007, 7:340-352.
2. Ferrara J.L., Levine J.E., Reddy P., et al. Graft-versus-host disease. Lancet 2009, 373:1550-1561.
3. Morecki S., Slavin S. Immunoregulation of GVHD by triggering the innate immune system with CpG. Expert Rev Hematol 2009, 2:443-453.
4. Bozdech M.J., Sondel P.M., Trigg M.E., et al. Transplantation of HLA-haploidentical T cell-depleted marrow for leukemia addition of cytosine arabinoside to the pretransplant conditioning prevents rejection. Exp Hematol 1985, 13:1201-1210.
5. Shalit M., Ayalon M., Weiss L., et al. Bone marrow transplantation with T-cell-depleted grafts, I: reconstitution of immunohemopoietic functions in lethally irradiated mice transplanted with unseparated or T-cell-depleted syngeneic bone marrow grafts. Transplantation 1986, 42:118-122.
6. Ash R.C., Horowitz M.M., Gale R.P., et al. Bone marrow transplantation from related donors other than HLA-identical siblings of T cell depletion. Bone Marrow Transplant 1991, 7:443-452.
7. Lenardo M., Chan K.M., Hornung F., et al. Mature T lymphocyte apoptosis: immune regulation in a dynamic and unpredictable antigenic environment. Annu Rev Immunol 1999, 17:221-253.
8. Hartwig U.F., Robbers M., Wickenhauser C., et al. Murine acute graft-versus-host disease can be prevented by depletion of alloreactive T lymphocytes using activation-induced cell death. Blood 2002, 99:3041-3049.
9. Georgantas R.W., Bohana-Kashtan O., Civin C.I. Ex vivo soluble fas ligand treatment of donor cells to selectively reduce murine acute graft-versus-host disease. Transplantation 2006, 82:471-478.
10. Bohana-Kashtan O., Morisot S., Hildreth R., et al. Selective reduction of graft-versus-host disease-mediating human T cells by ex vivo treatment with soluble Fas ligand. J Immunol 2009, 183:696-705.
11. Garderet L., Snell V., Przepiorka D., et al. Effective depletion of alloreactive lymphocytes from peripheral blood mononuclear cell preparations. Transplantation 1999, 61:124-130.
12. Vaclavkova P., Cao Y., Wu L.K., et al. A comparison of an anti-CD25 immunotoxin, Ontak and anti-CD25 microbeads for their ability to deplete alloreactive T cells in vitro. Bone Marrow Transplant 2006, 37:559-567.
13. Mavroudis D.A., Dermime S., Molldrem J., et al. Specific depletion of alloreactive T cells in HLA-identical siblings: a method for separating graft-versus-host and graft-versus-leukaemia reactions. Br J Haematol 1998, 101:565-570.
14. Montagna D., Yvon E., Calcaterra V., et al. Depletion of alloreactive T cells by a specific anti-interleukin-2 receptor p55 chain immunotoxin does not impair in vitro antileukemia and antiviral activity. Blood 1999, 93:3550-3557.
15. Amrolia P.J., Muccioli-Casadei G., Yvon E., et al. Selective depletion of donor alloreactive T cells without loss of antiviral or antileukemic responses. Blood 2003, 102:2292-2299.
16. Godfrey W.R., Krampf M.R., Taylor P.A., et al. Ex vivo depletion of alloreactive cells based on CFSE dye dilution, activation antigen selection, and dendritic cell stimulation. Blood 2004, 103:1158-1165.
17. Samarasinghe S., Mancao C., Pule M., et al. Functional characterization of alloreactive T cells identifies CD25 and CD71 as optimal targets for a clinically applicable allodepletion strategy. Blood 2010, 115:396-407.
18. Andre-Schmutz I., Le Deist F., Hacein-Bey-Abina S., et al. Immune reconstitution without graft-versus-host disease after haemopoietic stem-cell transplantation: a phase 1/2 study. Lancet 2002, 360:130-137.
19. Szabolcs P., Park K.D., Marti L., et al. Superior depletion of alloreactive T cells from peripheral blood stem cell and umbilical cord blood grafts by the combined use of trimetrexate and interleukin-2 immunotoxin. Biol Blood Marrow Transplant 2004, 10:772-783.
20. Amrolia P.J., Muccioli-Casadei G., Huls H., et al. Adoptive immunotherapy with allodepleted donor T-cells improves immune reconstitution after haploidentical stem cell transplantation. Blood 2006, 108:1797-1808.
21. + regulatory T cells (Tregs) after CD25-depleted allotransplantation in elderly patients and association with acute graft-versus-host disease. Blood 2007, 110:1689-1697.
22. Blaise D., Olive D., Hirn M., et al. Prevention of acute GVHD by in vivo use of anti-interleukin-2 receptor monoclonal antibody (33B3.1): a feasibility trial in 15 patients. Bone Marrow Transplant 1991, 8:105-111.
23. Chen H.R., Ji S.Q., Wang H.X., et al. Humanized anti-CD25 monoclonal antibody for prophylaxis of graft-vs-host disease (GVHD) in haploidentical bone marrow transplantation without ex vivo T-cell depletion. Exp Hematol 2003, 31:1019-1025.
24. Ji S.Q., Chen H.R., Yan H.M., et al. Anti-CD25 monoclonal antibody (basiliximab) for prevention of graft-versus-host disease after haploidentical bone marrow transplantation for hematological malignancies. Bone Marrow Transplant 2005, 36:349-354.
25. Kedar E., Tsuberi B.Z., Landesberg A., et al. In vitro and in vivo cytokine-induced facilitation of immunohematopoietic reconstitution in mice undergoing bone marrow transplantation. Bone Marrow Transplant 1988, 3:297-314.
26. Eckerstein A., Slavin S., Weiss L., et al. Immunotherapy in conjunction with autologous bone marrow transplantation. Bone Marrow Transplant 1990, 5(Suppl 1):38.
27. Szebeni J., Wang M.G., Pearson D.A., et al. IL-2 inhibits early increases in serum γ-interferon levels associated with graft-versus-host-disease. Transplantation 1994, 58:1385-1393.
28. Slavin S., Ackerstein A., Naparstek E., et al. The graft-versus-leukemia (GVL) phenomenon: is GVL separable from GVHD?. Bone Marrow Transplant 1990, 6:155-161.
29. Krenger W., Cooke K.R., Crawford J.M., et al. Transplantation of polarized type 2 donor T cells reduces mortality caused by experimental graft-versus-host disease. Transplantation 1996, 62:1278-1285.
30. + immunoregulatory T cells: new therapeutics for graft-versus-host disease. J Exp Med 2002, 196:401-406.
31. + regulatory T cells suppress lethal acute graft-versus-host disease after allogeneic bone marrow transplantation. J Exp Med 2002, 196:389-399.
32. + immune regulatory cells inhibits graft-versus-host disease lethality. Blood 2002, 99:3493-3499.
33. + regulatory T cells preserve graft-versus-tumor activity while inhibiting graft-versus-host disease after bone marrow transplantation. Nat Med 2003, 9:1144-1150.
34. + cells while preserving CD4- and CD8-mediated graft-versus-leukemia effects. Blood 1994, 83:2560-2569.
35. Shatry A., Levy R.B. In situ activation and expansion of host Tregs: a new approach to enhance donor chimerism and stable engraftment in major histocompatibility complex-matched allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 2009, 15:785-794.
36. + T cells. Blood 2010, 115:4934-4943.
37. Jiang Z., Adams G.B., Hanash A.M., et al. The contribution of cytotoxic and noncytotoxic function by donor T-cells that support engraftment after allogeneic bone marrow transplantation. Biol Blood Marrow Transplant 2002, 8:588-596.
38. Yarkoni S., Sagiv Y., Kaminitz A., et al. Targeted therapy to the IL-2R using diphtheria toxin and caspase-3 fusion proteins modulates Treg and ameliorates inflammatory colitis. Eur J Immunol 2009, 39:2850-2864.
39. Yarkoni S., Kaminitz A., Sagiv Y., et al. Targeting of IL-2 receptor with a caspase fusion protein disrupts autoimmunity in prediabetic and diabetic NOD mice. Diabetologia 2010, 53:356-368.
40. + T cells: a committed regulatory T-cell lineage and an uncommitted minor population retaining plasticity. Proc Natl Acad Sci USA 2009, 106:1903-1908.
41. Pearl-Yafe M., Yolcu E.S., Stein J., et al. Fas ligand enhances hematopoietic cell engraftment through abrogation of alloimmune responses and nonimmunogenic interactions. Stem Cells 2007, 25:1448-1455.
42. Prigozhina T.B., Elkin G., Khitrin S., et al. Prevention of acute graft-vs-host disease by a single low-dose cyclophosphamide injection following allogeneic bone marrow transplantation. Exp Hematol 2008, 36:1750-1759.
43. Ash S., Gigi V., Askenasy N., et al. Graft-versus-neuroblastoma reaction is efficiently elicited by allogeneic bone marrow transplantation through cytolytic activity in the absence of GVHD. Cancer Immunol Immunother 2009, 58:2073-2084.
44. + T cell subsets is dominated by cytokine deprivation and absence of other cells in new onset diabetic NOD mice. PLoS ONE 2010, 5:e15684.
45. Iwasaki T., Hamano T., Saheki K., et al. Effect of graft-versus-host disease (GVHD) on host hematopoietic progenitor cells is mediated by Fas-Fas ligand interactions, but this does not explain the effect of GVHD on donor cells. Cell Immunol 1999, 197:30-38.
46. Marks L., Altman N.H., Podack E.R., et al. Donor T cells lacking Fas ligand and perforin retain the capacity to induce severe GVHD in minor histocompatibility antigen mismatched bone-marrow transplantation recipients. Transplantation 2004, 77:804-812.
47. Teshima T., Mach N., Hill G.R., et al. Tumor cell vaccine elicits potent antitumor immunity after allogeneic T-cell-depleted bone marrow transplantation. Cancer Res 2001, 61:162-171.
48. Colson Y.L., Wren S.M., Schuchert M.J., et al. A nonlethal conditioning approach to achieve durable multilineage mixed chimerism and tolerance across major, minor, and hematopoietic histocompatibility barriers. J Immunol 1995, 155:4179-4188.
49. Prigozhina T.B., Elkin G., Khitrin S., et al. Depletion of donor-reactive cells as a new concept for improvement of mismatched bone marrow engraftment using reduced-intensity conditioning. Exp Hematol 2004, 32:1110-1117.
50. Siegel R.M., Chan F.K., Chun H.J., et al. The multifaceted role of Fas signaling in immune cell homeostasis and autoimmunity. Nat Immunol 2000, 1:469-474.
51. Lin J.X., Leonard W.J. Signaling from the IL-2 receptor to the nucleus. Cytokine Growth Factor Rev 1997, 8:313-332.
52. Willerford D.M., Chen J., Ferry J.A., et al. Interleukin-2 receptor α chain regulates the size and content of the peripheral lymphoid compartment. Immunity 1995, 3:521-530.
53. Kennedy N.J., Kataoka T., Tschopp J., et al. Caspase activation is required for T cell proliferation. J Exp Med 1999, 190:1891-1896.
54. + regulatory T cells. J Immunol 2004, 172:5287-5296.
55. Neurath M.F., Finotto S., Fuss I., et al. Regulation of T-cell apoptosis in inflammatory bowel disease: to die or not to die, that is the mucosal question. Trends Immunol 2001, 22:21-26.
56. Festjens N., van Gurp M., van Loo G., et al. Bcl-2 family members as sentinels of cellular integrity and role of mitochondrial intermembrane space proteins in apoptotic cell death. Acta Haematol 2004, 111:7-27.
57. Peppelenbosch M.P., van Deventer S.J. T cell apoptosis and inflammatory bowel disease. Gut 2004, 53:1556-1558.
58. + T regulatory cells. J Immunol 2006, 176:3301-3305.
59. Johnston J.A., Bacon C.M., Riedy M.C., et al. Signaling by IL-2 and related cytokines: JAKs, STATs, and relationship to immunodeficiency. J Leukoc Biol 1996, 60:441-452.
60. Kleinclauss F., Perruche S., Masson E., et al. Intravenous apoptotic spleen cell infusion induces a TGF-β-dependent regulatory T-cell expansion. Cell Death Differ 2006, 13:41-52.
61. McKinstry K.K., Golech S., Lee W.H., et al. Rapid default transition of CD4 T cell effectors to functional memory cells. J Exp Med 2007, 204:2199-2211.
62. Sabbagh L., Kaech S.M., Bourbonnière M., et al. The selective increase in caspase-3 expression in effector but not memory T cells allows susceptibility to apoptosis. J Immunol 2004, 173:5425-5433.
63. + T cells are defective in mediating acute graft-versus-host disease but retain graft-versus-leukemia activity. Blood 2004, 103:3970-3978.
64. + T cells do not induce graft-versus-host disease. J Clin Invest 2003, 112:101-108.
65. + T cell responses to Fas engagement. Proc Natl Acad Sci USA 1999, 96:8104-8109.
66. Strauss G., Knape I., Melzner I., et al. Constitutive caspase activation and impaired death-inducing signaling complex formation in CD95-resistant, long-term activated, antigen-specific T cells. J Immunol 2003, 171:1172-1182.
67. Zhang Y., Joe G., Hexner E., et al. Alloreactive memory T cells are responsible for the persistence of graft-versus-host disease. J Immunol 2005, 174:3051-3058.
68. Yaniv I., Ash S., Farkas D.L., et al. Consideration of strategies for hematopoietic cell transplantation. J Autoimmun 2009, 33:255-259.
69. + cells. Semin Immunol 2006, 18:78-88.
70. + T cells can expand and comprise a major component of the Treg compartment after experimental HCT. Blood 2009, 113:733-743.
71. + T regulatory cell-mediated suppression. Immunity 2009, 30:636-645.
72. Lan R.Y., Selmi C., Gershwin M.E. The regulatory, inflammatory, and T cell programming roles of interleukin-2 (IL-2). J Autoimmun 2008, 31:7-12.
73. Yarkoni S., Kaminitz A., Sagiv Y., et al. Involvement of IL-2 in homeostasis of regulatory T cells: the IL-2 cycle. Bioessays 2008, 30:875-888.
74. Askenasy E.M., Askenasy N., Askenasy J.J. Does lymphopenia preclude restoration of immune homeostasis? The particular case of type 1 diabetes. Autoimmun Rev 2010, 9:687-690.
75. Barthlott T., Kassiotis G., Stockinger B. T cell regulation as a side effect of homeostasis and competition. J Exp Med 2003, 197:451-460.
76. + regulatory T cells. Nat Med 2005, 11:1238-1243.
77. Abdul-Hai A., Weiss L., Slavin S., et al. Improved survival following induction of GVHD following lipopolysaccharide immunization. Exp Hematol 2006, 34:549-553.
78. Morecki S., Yacovlev E., Gelfand Y., et al. Pretransplant treatment of donors with immunomodulators to control graft-versus-host disease (GVHD) in transplant recipients. Exp Hematol 2007, 35:748-756.
79. Panigrahi S., Morecki S., Yacovlev E., et al. A novel approach for prevention of lethal GVHD by selective elimination of alloreactive donor lymphocytes prior to stem cell transplantation. Exp Hematol 2004, 32:756-764.