Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

T cell therapies following hematopoietic stem cell transplantation: surely there must be a better way than DLI?

Abstract

Advances in the past few years have significantly improved adoptive immunotherapy strategies available following autologous and allogeneic hematopoietic stem cell transplantation (HSCT). Minimal residual disease, relapsed disease and viral infections remain a significant cause of mortality in patients undergoing HSCT. Novel therapies are critically needed to overcome these management dilemmas, while sparing the graft-versus-tumor effect and avoiding graft-versus-host disease. This review focuses on the T-cell strategies currently available to allay disease while minimizing toxicities in patients who have undergone HSCT.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Van den Eynde B, Brichard VG . New tumor antigens recognized by T cells. Current Opin Imunol 1995; 7: 674–681.

    Article  CAS  Google Scholar 

  2. Yee C, Gilbert MJ, Riddell SR, Brichard VG, Fefer A, Thompson JA et al. Isolation of tyrosinase-specific CD8+ and CD4+ T cell clones from the peripheral blood of melanoma patients following in vitro stimulation with recombinant vaccinia virus. J Immunol 1996; 157: 4079–4086.

    CAS  PubMed  Google Scholar 

  3. Thirdborough SM, Radcliffe JN, Friedmann PS, Stevenson FK . Vaccination with DNA encoding a single-chain TCR fusion protein induces anticlonotypic immunity and protects against T cell lymphoma. Cancer Res 2002; 62: 1757–1760.

    CAS  PubMed  Google Scholar 

  4. Marijt WA, Heemskerk MH, Kloosterboer FM, Goulmy E, Kester MG, van der Hoorn MA et al. Hematopoiesis-restricted minor histocompatibility antigens HA-1- or HA-2-specific T cells can induce complete remissions of relapsed leukemia. Proc Natl Acad Sci USA 2003; 100: 2742–2747.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kloosterboer FM, van Luxemburg-Heijs SA, van Soest RA, van Egmond HM, Barbui AM, Strijbosch MP et al. Minor histocompatibility antigen-specific T cells with multiple distinct specificities can be isolated by direct cloning of IFNgamma-secreting T cells from patients with relapsed leukemia responding to donor lymphocyte infusion. Leukemia 2005; 19: 83–90.

    Article  CAS  PubMed  Google Scholar 

  6. Falkenburg JH, van de Corp L, Marijt EW, Willemze R . Minor histocompatibility antigens in human stem cell transplantation. Exp Hematol 2003; 31: 743–751.

    Article  CAS  PubMed  Google Scholar 

  7. Dickinson AM, Wang XN, Sviland L, Vyth-Dreese FA, Jackson GH, Schumacher TN et al. In situ dissection of the graft-versus-host activities of cytotoxic T cells specific for minor histocompatibility antigens. Nat Med 2002; 8: 410–414.

    Article  CAS  PubMed  Google Scholar 

  8. Goulmy E . Minor histocompatibility antigens: from transplantation problems to therapy of cancer. Hum Immunol 2006; 67: 433–438.

    Article  CAS  PubMed  Google Scholar 

  9. Zendman AJ, Ruiter DJ, Van Muijen GN . Cancer/testis-associated genes: identification, expression profile, and putative function. J Cell Physiol 2003; 194: 272–288.

    Article  CAS  PubMed  Google Scholar 

  10. Liggins AP, Guinn BA, Banham AH . Identification of lymphoma-associated antigens using SEREX. Methods Mol Med 2005; 115: 109–128.

    CAS  PubMed  Google Scholar 

  11. Haffner AC, Tassis A, Zepter K, Storz M, Tureci O, Burg G et al. Expression of cancer/testis antigens in cutaneous T cell lymphomas. Int J Cancer 2002; 97: 668–670.

    Article  CAS  PubMed  Google Scholar 

  12. Liggins AP, Guinn BA, Hatton CS, Pulford K, Banham AH . Serologic detection of diffuse large B-cell lymphoma-associated antigens. Int J Cancer 2004; 110: 563–569.

    Article  CAS  PubMed  Google Scholar 

  13. Atanackovic D, Arfsten J, Cao Y, Gnjatic S, Schnieders F, Bartels K et al. Cancer-testis antigens are commonly expressed in multiple myeloma and induce systemic immunity following allogeneic stem cell transplantation. Blood 2007; 109: 1103–1112.

    Article  CAS  PubMed  Google Scholar 

  14. van RF, Szmania SM, Zhan F, Gupta SK, Pomtree M, Lin P et al. NY-ESO-1 is highly expressed in poor-prognosis multiple myeloma and induces spontaneous humoral and cellular immune responses. Blood 2005; 105: 3939–3944.

    Article  CAS  Google Scholar 

  15. Szmania S, Tricot G, van RF . NY-ESO-1 immunotherapy for multiple myeloma. Leuk Lymphoma 2006; 47: 2037–2048.

    Article  CAS  PubMed  Google Scholar 

  16. Molldrem JJ, Lee PP, Wang C, Champlin RE, Davis MM . A PR1-human leukocyte antigen-A2 tetramer can be used to isolate low-frequency cytotoxic T lymphocytes from healthy donors that selectively lyse chronic myelogenous leukemia. Cancer Res 1999; 59: 2675–2681.

    CAS  PubMed  Google Scholar 

  17. Heslop HE, Stevenson FK, Molldrem JJ . Immunotherapy of hematologic malignancy. Hematol Am Soc Hematol Educ Program 2003, 331–349.

    Article  Google Scholar 

  18. Greiner J, Schmitt M, Li L, Giannopoulos K, Bosch K, Schmitt A et al. Expression of tumor-associated antigens in acute myeloid leukemia: Implications for specific immunotherapeutic approaches. Blood 2006; 108: 4109–4117.

    Article  CAS  PubMed  Google Scholar 

  19. Bocchia M, Wentworth PA, Southwood S, Sidney J, McGraw K, Scheinberg DA et al. Specific binding of leukemia oncogene fusion protein peptides to HLA class I molecules. Blood 1995; 85: 2680–2684.

    Article  CAS  PubMed  Google Scholar 

  20. Yotnda P, Firat H, Garcia-Pons F, Garcia Z, Gourru G, Vernant JP et al. Cytotoxic T cell response against the chimeric p210 BCR–ABL protein in patients with chronic myelogenous leukemia. J Clin Invest 1998; 101: 2290–2296.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Osman Y, Takahashi M, Zheng Z, Koike T, Toba K, Liu A et al. Generation of BCR–ABL specific cytotoxic T-lymphocytes by using dendritic cells pulsed with bcr-abl (b3a2) peptide: its applicability for donor leukocyte transfusions in marrow grafted CML patients. Leukemia 1999; 13: 166–174.

    Article  CAS  PubMed  Google Scholar 

  22. Young LS, Rickinson AB . Epstein-Barr virus: 40 years on. Nat Rev Cancer 2004; 4: 757–768.

    Article  CAS  PubMed  Google Scholar 

  23. Cohen JI . Benign and malignant Epstein–Barr virus-associated B-cell lymphoproliferative diseases. Semin Hematol 2003; 40: 116–123.

    Article  PubMed  Google Scholar 

  24. Gottschalk S, Heslop HE, Rooney CM . Adoptive immunotherapy for EBV-associated malignancies. Leuk Lymphoma 2005; 46: 1–10.

    Article  CAS  PubMed  Google Scholar 

  25. Kolb HJ, Schattenberg A, Goldman JM, Hertenstein B, Jacobsen N, Arcese W et al. Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients. European Group for Blood and Marrow Transplantation Working Party Chronic Leukemia. Blood 1995; 86: 2041–2050.

    Article  CAS  PubMed  Google Scholar 

  26. Collins Jr RH, Shpilberg O, Drobyski WR, Porter DL, Giralt S, Champlin R et al. Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation. J Clin Oncol 1997; 15: 433–444.

    Article  PubMed  Google Scholar 

  27. Kolb HJ, Schmid C, Barrett AJ, Schendel DJ . Graft-versus-leukemia reactions in allogeneic chimeras. Blood 2004; 103: 767–776.

    Article  CAS  PubMed  Google Scholar 

  28. Mackinnon S, Papadopoulos EB, Carabasi MH, Reich L, Collins NH, O’Reilly RJ . Adoptive immunotherapy using donor leukocytes following bone marrow transplantation for chronic myeloid leukemia: is T cell dose important in determining biological response? Bone Marrow Transplant 1995; 15: 591–594.

    CAS  PubMed  Google Scholar 

  29. Giralt SA, Kolb HJ . Donor lymphocyte infusions. Curr Opin Oncol 1996; 8: 96–102.

    Article  CAS  PubMed  Google Scholar 

  30. Kolb HJ, Holler E . Adoptive immunotherapy with donor lymphocyte transfusions. Curr Opin Oncol 1997; 9: 139–145.

    Article  CAS  PubMed  Google Scholar 

  31. Weisser M, Tischer J, Schnittger S, Schoch C, Ledderose G, Kolb HJ . A comparison of donor lymphocyte infusions or imatinib mesylate for patients with chronic myelogenous leukemia who have relapsed after allogeneic stem cell transplantation. Haematologica 2006; 91: 663–666.

    CAS  PubMed  Google Scholar 

  32. Choi SJ, Lee JH, Lee JH, Kim S, Lee YS, Seol M et al. Treatment of relapsed acute lymphoblastic leukemia after allogeneic bone marrow transplantation with chemotherapy followed by G-CSF-primed donor leukocyte infusion: a prospective study. Bone Marrow Transplant 2005; 36: 163–169.

    Article  CAS  PubMed  Google Scholar 

  33. Papadopoulos EB, Ladanyi M, Emanuel D, Mackinnon S, Boulad F, Carabasi MH et al. Infusions of donor leukocytes to treat Epstein–Barr virus-associated lymphoproliferative disorders after allogeneic bone marrow transplantation. N Engl J Med 1994; 330: 1185–1191.

    Article  CAS  PubMed  Google Scholar 

  34. O’Reilly RJ, Small TN, Papadopoulos E, Lucas K, Lacerda J, Koulova L . Adoptive immunotherapy for Epstein–Barr virus-associated lymphoproliferative disorders complicating marrow allografts. Springer Semin Immunopathol 1998; 20: 455–491.

    Article  PubMed  Google Scholar 

  35. Lucas KG, Burton RL, Zimmerman SE, Wang J, Cornetta KG, Robertson KA et al. Semiquantitative Epstein-Barr virus (EBV) polymerase chain reaction for the determination of patients at risk for EBV-induced lymphoproliferative disease after stem cell transplantation. Blood 1998; 91: 3654–3661.

    Article  CAS  PubMed  Google Scholar 

  36. Mandigers CM, Verdonck LF, Meijerink JP, Dekker AW, Schattenberg AV, Raemaekers JM . Graft-versus-lymphoma effect of donor lymphocyte infusion in indolent lymphomas relapsed after allogeneic stem cell transplantation. Bone Marrow Transplant 2003; 32: 1159–1163.

    Article  CAS  PubMed  Google Scholar 

  37. Russell NH, Byrne JL, Faulkner RD, Gilyead M, Das-Gupta EP, Haynes AP . Donor lymphocyte infusions can result in sustained remissions in patients with residual or relapsed lymphoid malignancy following allogeneic haemopoietic stem cell transplantation. Bone Marrow Transplant 2005; 36: 437–441.

    Article  CAS  PubMed  Google Scholar 

  38. Marks DI, Lush R, Cavenagh J, Milligan DW, Schey S, Parker A et al. The toxicity and efficacy of donor lymphocyte infusions given after reduced-intensity conditioning allogeneic stem cell transplantation. Blood 2002; 100: 3108–3114.

    Article  CAS  PubMed  Google Scholar 

  39. Morris E, Thomson K, Craddock C, Mahendra P, Milligan D, Cook G et al. Outcomes after alemtuzumab-containing reduced-intensity allogeneic transplantation regimen for relapsed and refractory non-Hodgkin lymphoma. Blood 2004; 104: 3865–3871.

    Article  CAS  PubMed  Google Scholar 

  40. Gajewski JL, Phillips GL, Sobocinski KA, Armitage JO, Gale RP, Champlin RE et al. Bone marrow transplants from HLA-identical siblings in advanced Hodgkin's disease. J Clin Oncol 1996; 14: 572–578.

    Article  CAS  PubMed  Google Scholar 

  41. Milpied N, Fielding AK, Pearce RM, Ernst P, Goldstone AH . Allogeneic bone marrow transplant is not better than autologous transplant for patients with relapsed Hodgkin's disease. European Group for Blood and Bone Marrow Transplantation. J Clin Oncol 1996; 14: 1291–1296.

    Article  CAS  PubMed  Google Scholar 

  42. Peggs KS, Hunter A, Chopra R, Parker A, Mahendra P, Milligan D et al. Clinical evidence of a graft-versus-Hodgkin's-lymphoma effect after reduced-intensity allogeneic transplantation. Lancet 2005; 365: 1934–1941.

    Article  PubMed  Google Scholar 

  43. Anderlini P, Acholonu SA, Okoroji GJ, Andersson BS, Couriel DR, De Lima MJ et al. Donor leukocyte infusions in relapsed Hodgkin's lymphoma following allogeneic stem cell transplantation: CD3+ cell dose, GVHD and disease response. Bone Marrow Transplant 2004; 34: 511–514.

    Article  CAS  PubMed  Google Scholar 

  44. Lokhorst HM, Schattenberg A, Cornelissen JJ, Thomas LL, Verdonck LF . Donor leukocyte infusions are effective in relapsed multiple myeloma after allogeneic bone marrow transplantation. Blood 1997; 90: 4206–4211.

    Article  CAS  PubMed  Google Scholar 

  45. Lokhorst HM, Schattenberg A, Cornelissen JJ, van Oers MH, Fibbe W, Russell I et al. Donor lymphocyte infusions for relapsed multiple myeloma after allogeneic stem-cell transplantation: predictive factors for response and long-term outcome. J Clin Oncol 2000; 18: 3031–3037.

    Article  CAS  PubMed  Google Scholar 

  46. van de Donk NW, Kroger N, Hegenbart U, Corradini P, San Miguel JF, Goldschmidt H et al. Prognostic factors for donor lymphocyte infusions following non-myeloablative allogeneic stem cell transplantation in multiple myeloma. Bone Marrow Transplant 2006; 37: 1135–1141.

    Article  CAS  PubMed  Google Scholar 

  47. Bertz H, Burger JA, Kunzmann R, Mertelsmann R, Finke J . Adoptive immunotherapy for relapsed multiple myeloma after allogeneic bone marrow transplantation (BMT): evidence for a graft-versus-myeloma effect. Leukemia 1997; 11: 281–283.

    Article  CAS  PubMed  Google Scholar 

  48. Salama M, Nevill T, Marcellus D, Parker P, Johnson M, Kirk A et al. Donor leukocyte infusions for multiple myeloma. Bone Marrow Transplant 2000; 26: 1179–1184.

    Article  CAS  PubMed  Google Scholar 

  49. Peggs KS, Mackinnon S, Williams CD, D’Sa S, Thuraisundaram D, Kyriakou C et al. Reduced-intensity transplantation with in vivo T cell depletion and adjuvant dose-escalating donor lymphocyte infusions for chemotherapy-sensitive myeloma: limited efficacy of graft-versus-tumor activity. Biol Blood Marrow Transplant 2003; 9: 257–265.

    Article  PubMed  Google Scholar 

  50. Peggs KS, Thomson K, Hart DP, Geary J, Morris EC, Yong K et al. Dose-escalated donor lymphocyte infusions following reduced intensity transplantation: toxicity, chimerism, and disease responses. Blood 2004; 103: 1548–1556.

    Article  CAS  PubMed  Google Scholar 

  51. Shimoni A, Gajewski JA, Donato M, Martin T, O’Brien S, Talpaz M et al. Long-term follow-up of recipients of CD8-depleted donor lymphocyte infusions for the treatment of chronic myelogenous leukemia relapsing after allogeneic progenitor cell transplantation. Biol Blood Marrow Transplant 2001; 7: 568–575.

    Article  CAS  PubMed  Google Scholar 

  52. Champlin R, Ho W, Gajewski J, Feig S, Burnison M, Holley G et al. Selective depletion of CD8+ T lymphocytes for prevention of graft-versus-host disease after allogeneic bone marrow transplantation. Blood 1990; 76: 418–423.

    Article  CAS  PubMed  Google Scholar 

  53. Alyea EP, Canning C, Neuberg D, Daley H, Houde H, Giralt S et al. CD8+ cell depletion of donor lymphocyte infusions using cd8 monoclonal antibody-coated high-density microparticles (CD8-HDM) after allogeneic hematopoietic stem cell transplantation: a pilot study. Bone Marrow Transplant 2004; 34: 123–128.

    Article  CAS  PubMed  Google Scholar 

  54. Amrolia PJ, Mucioli-Casadei G, Huls H, Heslop HE, Schindler J, Veys P et al. Add-back of allodepleted donor T cells to improve immune reconstitution after haplo-identical stem cell transplantation. Cytotherapy 2005; 7: 116–125.

    Article  CAS  PubMed  Google Scholar 

  55. Solomon SR, Tran T, Carter CS, Donnelly S, Hensel N, Schindler J et al. Optimized clinical-scale culture conditions for ex vivo selective depletion of host-reactive donor lymphocytes: a strategy for GvHD prophylaxis in allogeneic PBSC transplantation. Cytotherapy 2002; 4: 395–406.

    Article  CAS  PubMed  Google Scholar 

  56. Amrolia PJ, Muccioli-Casadei G, Huls H, Adams S, Durett A, Gee A et al. Adoptive immunotherapy with allodepleted donor T cells improves immune reconstitution after haploidentical stem cell transplantation. Blood 2006; 108: 1797–1808.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Alyea EP, Soiffer RJ, Canning C, Neuberg D, Schlossman R, Pickett C et al. Toxicity and efficacy of defined doses of CD4(+) donor lymphocytes for treatment of relapse after allogeneic bone marrow transplant. Blood 1998; 91: 3671–3680.

    Article  CAS  PubMed  Google Scholar 

  58. Giralt S, Hester J, Huh Y, Hirsch-Ginsberg C, Rondon G, Seong D et al. CD8-depleted donor lymphocyte infusion as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation. Blood 1995; 86: 4337–4343.

    Article  CAS  PubMed  Google Scholar 

  59. Fowler D, Hou J, Foley J, Hakim F, Odom J, Castro K et al. Phase I clinical trial of donor T-helper type-2 cells after immunoablative, reduced intensity allogeneic PBSC transplant. Cytotherapy 2002; 4: 429–430.

    Article  CAS  PubMed  Google Scholar 

  60. Fowler DH, Odom J, Steinberg SM, Chow CK, Foley J, Kogan Y et al. Phase I clinical trial of costimulated, IL-4 polarized donor CD4+ T cells as augmentation of allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 2006; 12: 1150–1160.

    Article  CAS  PubMed  Google Scholar 

  61. Bonini C, Ferrari G, Verzeletti S, Servida P, Zappone E, Ruggieri L et al. HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia. Science 1997; 276: 1719–1724.

    Article  CAS  PubMed  Google Scholar 

  62. Tiberghien P, Ferrand C, Lioure B, Milpied N, Angonin R, Deconinck E et al. Administration of herpes simplex-thymidine kinase-expressing donor T cells with a T cell-depleted allogeneic marrow graft. Blood 2001; 97: 63–72.

    Article  CAS  PubMed  Google Scholar 

  63. Burt RK, Drobyski WR, Seregina T, Traynor A, Oyama Y, Keever-Taylor C et al. Herpes simplex thymidine kinase gene-transduced donor lymphocyte infusions. Exp Hematol 2003; 31: 903–910.

    Article  CAS  PubMed  Google Scholar 

  64. Berger C, Flowers ME, Warren EH, Riddell SR . Analysis of transgene-specific immune responses that limit the in vivo persistence of adoptively transferred HSV-TK-modified donor T cells after allogeneic hematopoietic cell transplantation. Blood 2006; 107: 2294–2302.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Sauce D, Bodinier M, Garin M, Petracca B, Tonnelier N, Duperrier A et al. Retrovirus-mediated gene transfer in primary T lymphocytes impairs their anti-Epstein–Barr virus potential through both culture-dependent and selection process-dependent mechanisms. Blood 2002; 99: 1165–1173.

    Article  CAS  PubMed  Google Scholar 

  66. Marktel S, Magnani Z, Ciceri F, Cazzaniga S, Riddell SR, Traversari C et al. Immunologic potential of donor lymphocytes expressing a suicide gene for early immune reconstitution after hematopoietic T cell-depleted stem cell transplantation. Blood 2003; 101: 1290–1298.

    Article  CAS  PubMed  Google Scholar 

  67. Thomis DC, Marktel S, Bonini C, Traversari C, Gilman M, Bordignon C et al. A Fas-based suicide switch in human T cells for the treatment of graft-versus-host disease. Blood 2001; 97: 1249–1257.

    Article  CAS  PubMed  Google Scholar 

  68. Straathof KC, Pule MA, Yotnda P, Dotti G, Vanin EF, Brenner MK et al. An inducible caspase 9 safety switch for T cell therapy. Blood 2005; 105: 4247–4254.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Porrata LF, Litzow MR, Tefferi A, Letendre L, Kumar S, Geyer SM et al. Early lymphocyte recovery is a predictive factor for prolonged survival after autologous hematopoietic stem cell transplantation for acute myelogenous leukemia. Leukemia 2002; 16: 1311–1318.

    Article  CAS  PubMed  Google Scholar 

  70. Porrata LF, Inwards DJ, Micallef IN, Ansell SM, Geyer SM, Markovic SN . Early lymphocyte recovery post-autologous haematopoietic stem cell transplantation is associated with better survival in Hodgkin's disease. Br J Haematol 2002; 117: 629–633.

    Article  PubMed  Google Scholar 

  71. Porrata LF, Gertz MA, Inwards DJ, Litzow MR, Lacy MQ, Tefferi A et al. Early lymphocyte recovery predicts superior survival after autologous hematopoietic stem cell transplantation in multiple myeloma or non-Hodgkin's lymphoma. Blood 2001; 98: 579–585.

    Article  CAS  PubMed  Google Scholar 

  72. Laport GG, Levine BL, Stadtmauer EA, Schuster SJ, Luger SM, Grupp S et al. Adoptive transfer of costimulated T cells induces lymphocytosis in patients with relapsed/refractory non-Hodgkin lymphoma following CD34+-selected hematopoietic cell transplantation. Blood 2003; 102: 2004–2013.

    Article  CAS  PubMed  Google Scholar 

  73. Porter DL, Levine BL, Bunin N, Stadtmauer EA, Luger SM, Goldstein S et al. A phase 1 trial of donor lymphocyte infusions expanded and activated ex vivo via CD3/CD28 costimulation. Blood 2006; 107: 1325–1331.

    Article  CAS  PubMed  Google Scholar 

  74. Kornacker M, Moldenhauer G, Herbst M, Weilguni E, Tita-Nwa F, Harter C et al. Cytokine-induced killer cells against autologous CLL: direct cytotoxic effects and induction of immune accessory molecules by interferon-gamma. Int J Cancer 2006; 119: 1377–1382.

    Article  CAS  PubMed  Google Scholar 

  75. Lefterova P, Schakowski F, Buttgereit P, Scheffold C, Huhn D, Schmidt-Wolf IG . Expansion of CD3+ CD56+ cytotoxic cells from patients with chronic lymphocytic leukemia: in vitro efficacy. Haematologica 2000; 85: 1108–1109.

    CAS  PubMed  Google Scholar 

  76. Linn YC, Lau LC, Hui KM . Generation of cytokine-induced killer cells from leukaemic samples with in vitro cytotoxicity against autologous and allogeneic leukaemic blasts. Br J Haematol 2002; 116: 78–86.

    Article  CAS  PubMed  Google Scholar 

  77. Leemhuis T, Wells S, Scheffold C, Edinger M, Negrin RS . A phase I trial of autologous cytokine-induced killer cells for the treatment of relapsed Hodgkin disease and non-Hodgkin lymphoma. Biol Blood Marrow Transplant 2005; 11: 181–187.

    Article  PubMed  Google Scholar 

  78. Introna M, Franceschetti M, Ciocca A, Borleri G, Conti E, Golay J et al. Rapid and massive expansion of cord blood-derived cytokine-induced killer cells: an innovative proposal for the treatment of leukemia relapse after cord blood transplantation. Bone Marrow Transplant 2006; 38: 621–627.

    Article  CAS  PubMed  Google Scholar 

  79. Walter EA, Greenberg PD, Gilbert MJ, Finch RJ, Watanabe KS, Thomas ED et al. Reconstitution of cellular immunity against cytomegalovirus in recipients of allogeneic bone marrow by transfer of T cell clones from the donor. N Engl J Med 1995; 333: 1038–1044.

    Article  CAS  PubMed  Google Scholar 

  80. Gottschalk S, Heslop HE, Rooney CM . Treatment of Epstein-Barr virus-associated malignancies with specific T cells. Adv Cancer Res 2002; 84: 175–201.

    Article  CAS  PubMed  Google Scholar 

  81. Lanzavecchia A, Sallusto F . Antigen decoding by T lymphocytes: from synapses to fate determination. Nat Immunol 2001; 2: 487–492.

    Article  CAS  PubMed  Google Scholar 

  82. Wagner HJ, Rooney CM, Heslop HE . Diagnosis and treatment of posttransplantation lymphoproliferative disease after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2002; 8: 1–8.

    Article  CAS  PubMed  Google Scholar 

  83. Kuehnle I, Huls MH, Liu Z, Semmelmann M, Krance RA, Brenner MK et al. CD20 monoclonal antibody (rituximab) for therapy of Epstein-Barr virus lymphoma after hemopoietic stem-cell transplantation. Blood 2000; 95: 1502–1505.

    Article  CAS  PubMed  Google Scholar 

  84. Davis TA, Czerwinski DK, Levy R . Therapy of B-cell lymphoma with anti-CD20 antibodies can result in the loss of CD20 antigen expression (in process citation). Clin Cancer Res 1999; 5: 611–615.

    CAS  PubMed  Google Scholar 

  85. Heslop HE, Ng CY, Li C, Smith CA, Loftin SK, Krance RA et al. Long-term restoration of immunity against Epstein–Barr virus infection by adoptive transfer of gene-modified virus-specific T lymphocytes. Nat Med 1996; 2: 551–555.

    Article  CAS  PubMed  Google Scholar 

  86. Rooney CM, Smith CA, Ng CYC, Loftin SK, Sixbey JW, Gan Y-J et al. Infusion of cytotoxic T cells for the prevention and treatment of Epstein–Barr virus-induced lymphoma in allogeneic transplant recipients. Blood 1998; 92: 1549–1555.

    Article  CAS  PubMed  Google Scholar 

  87. Gottschalk S, Rooney CM, Heslop HE . Post-transplant lymphoproliferative disorders. Annu Rev Med 2005; 56: 29–44.

    Article  CAS  PubMed  Google Scholar 

  88. Pule M, Rousseau A, Bollard C, Brenner MK, Rooney CM, Heslop HE . Long-term safety and persistance data after infusion of retrovirally marked EBV-CTLs [abstract]. Blood 2003; 102: 745a.

    Google Scholar 

  89. Gottschalk S, Ng CY, Perez M, Smith CA, Sample C, Brenner MK et al. An Epstein–Barr virus deletion mutant associated with fatal lymphoproliferative disease unresponsive to therapy with virus-specific CTLs. Blood 2001; 97: 835–843.

    Article  CAS  PubMed  Google Scholar 

  90. Straathof KC, Leen AM, Buza EL, Taylor G, Huls MH, Heslop HE et al. Characterization of latent membrane protein 2 specificity in CTL lines from patients with EBV-positive nasopharyngeal carcinoma and lymphoma. J Immunol 2005; 175: 4137–4147.

    Article  CAS  PubMed  Google Scholar 

  91. Bollard CM, Huls MH, Buza E, Weiss H, Torrano V, Gresik MV et al. Administration of latent membrane protein 2-specific cytotoxic T lymphocytes to patients with relapsed Epstein-Barr virus-positive lymphoma. Clin Lymphoma Myeloma 2006; 6: 342–347.

    Article  CAS  PubMed  Google Scholar 

  92. Riddell SR, Watanabe KS, Goodrich JM, Li CR, Agha ME, Greenberg PD . Restoration of viral immunity in immunodeficient humans by the adoptive transfer of T cell clones. Science 1992; 257: 238–241.

    Article  CAS  PubMed  Google Scholar 

  93. Rooney CM, Smith CA, Ng CY, Loftin S, Li C, Krance RA et al. Use of gene-modified virus-specific T lymphocytes to control Epstein–Barr-virus-related lymphoproliferation. Lancet 1995; 345: 9–13.

    Article  CAS  PubMed  Google Scholar 

  94. Bollard CM, Kuehnle I, Leen A, Rooney CM, Heslop HE . Adoptive immunotherapy for posttransplantation viral infections. Biol Blood Marrow Transplant 2004; 10: 143–155.

    Article  CAS  PubMed  Google Scholar 

  95. Feuchtinger T, Matthes-Martin S, Richard C, Lion T, Fuhrer M, Hamprecht K et al. Safe adoptive transfer of virus-specific T cell immunity for the treatment of systemic adenovirus infection after allogeneic stem cell transplantation. Br J Haematol 2006; 134: 64–76.

    Article  PubMed  Google Scholar 

  96. Leen AM, Myers GD, Sili U, Huls MH, Weiss H, Leung KS et al. Monoculture-derived T lymphocytes specific for multiple viruses expand and produce clinically relevant effects in immunocompromised individuals. Nat Med 2006; 12: 1160–1166.

    Article  CAS  PubMed  Google Scholar 

  97. Johnson LA, Heemskerk B, Powell Jr DJ, Cohen CJ, Morgan RA, Dudley ME et al. Gene transfer of tumor-reactive TCR confers both high avidity and tumor reactivity to nonreactive peripheral blood mononuclear cells and tumor-infiltrating lymphocytes. J Immunol 2006; 177: 6548–6559.

    Article  CAS  PubMed  Google Scholar 

  98. Dudley ME, Wunderlich J, Nishimura MI, Yu D, Yang JC, Topalian SL et al. Adoptive transfer of cloned melanoma-reactive T lymphocytes for the treatment of patients with metastatic melanoma. J Immunother 2001; 24: 363–373.

    Article  CAS  PubMed  Google Scholar 

  99. Dudley ME, Wunderlich JR, Yang JC, Sherry RM, Topalian SL, Restifo NP et al. Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J Clin Oncol 2005; 23: 2346–2357.

    Article  CAS  PubMed  Google Scholar 

  100. Powell Jr DJ, Dudley ME, Hogan KA, Wunderlich JR, Rosenberg SA . Adoptive transfer of vaccine-induced peripheral blood mononuclear cells to patients with metastatic melanoma following lymphodepletion. J Immunol 2006; 177: 6527–6539.

    Article  CAS  PubMed  Google Scholar 

  101. Morgan RA, Dudley ME, Wunderlich JR, Hughes MS, Yang JC, Sherry RM et al. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 2006; 314: 126–129.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Amrolia PJ, Mucioli-Casadei G, Huls H, Heslop HE, Schindler J, Veys P et al. Add-back of allodepleted donor T cells to improve immune reconstitution after haplo-identical stem cell transplantation. Cytotherapy 2005; 7: 116–125.

    Article  CAS  PubMed  Google Scholar 

  103. Amrolia PJ, Muccioli-Casadei G, Huls H, Adams S, Durett A, Gee A et al. Adoptive immunotherapy with allodepleted donor T cells improves immune reconstitution after haploidentical stem cell transplantation. Blood 2006; 108: 1797–1808.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Andre-Schmutz I, Le Deist F, Hacein-Bey-Abina S, Vitetta E, Schindler J, Chedeville G et al. Immune reconstitution without graft-versus-host disease after haemopoietic stem-cell transplantation: a phase 1/2 study. Lancet 2002; 360: 130–137.

    Article  PubMed  Google Scholar 

  105. Gustafsson A, Levitsky V, Zou JZ, Frisan T, Dalianis T, Ljungman P et al. Epstein–Barr virus (EBV) load in bone marrow transplant recipients at risk to develop posttransplant lymphoproliferative disease: prophylactic infusion of EBV-specific cytotoxic T cells. Blood 2000; 95: 807–814.

    Article  CAS  PubMed  Google Scholar 

  106. Heslop HE, Brenner MK, Rooney CM . Donor T cells to treat EBV-associated lymphoma. N Engl J Med 1994; 331: 679–680.

    Article  CAS  PubMed  Google Scholar 

  107. Bollard CM, Huls MH, Buza E, Weiss H, Torrano V, Gresik MV et al. Administration of latent membrane protein 2-specific cytotoxic T lymphocytes to patients with relapsed Epstein-Barr virus-positive lymphoma. Clin Lymphoma Myeloma 2006; 6: 342–347.

    Article  CAS  PubMed  Google Scholar 

  108. Einsele H, Roosnek E, Rufer N, Sinzger C, Riegler S, Loffler J et al. Infusion of cytomegalovirus (CMV)-specific T cells for the treatment of CMV infection not responding to antiviral chemotherapy. Blood 2002; 99: 3916–3922.

    Article  CAS  PubMed  Google Scholar 

  109. Cobbold M, Khan N, Pourgheysari B, Tauro S, McDonald D, Osman H et al. Adoptive transfer of cytomegalovirus-specific CTL to stem cell transplant patients after selection by HLA-peptide tetramers. J Exp Med 2005; 202: 379–386.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Qazilbash MH, Wieder E, Rios R, Sijie L, Kant S, Giralt S et al. Vaccination with the PR 1 eukemia-associated antigen can induce complete remission in patients with myeloid leukemia. (abstract). Blood 2004; 104 Abstract 259.

  111. Fowler DH, Bishop MR, Gress RE . Immunoablative reduced-intensity stem cell transplantation: potential role of donor Th2 and Tc2 cells. Semin Oncol 2004; 31: 56–67.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to C M Bollard.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kennedy-Nasser, A., Bollard, C. T cell therapies following hematopoietic stem cell transplantation: surely there must be a better way than DLI?. Bone Marrow Transplant 40, 93–104 (2007). https://doi.org/10.1038/sj.bmt.1705667

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1705667

Keywords

Search

Quick links