Strategies to accelerate immune recovery after allogeneic hematopoietic stem cell transplantation

References

• Copelan EA. Hematopoietic stem-cell transplantation. N Engl J Med. 2006;354(17):1813–1826.
   PubMed Web of Science ®Google Scholar
• Aversa F, Tabilio A, Velardi A, et al. Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype. N Engl J Med. 1998;339(17):1186–1193.
   PubMed Web of Science ®Google Scholar
• Ciceri F, Labopin M, Aversa F, et al. A survey of fully haploidentical hematopoietic stem cell transplantation in adults with high-risk acute leukemia: a risk factor analysis of outcomes for patients in remission at transplantation. Blood. 2008;112(9):3574–3581.
   PubMed Web of Science ®Google Scholar
• Locatelli F, Vinti L, Palumbo G, et al. Strategies to optimize the outcome of children given T-cell depleted HLA-haploidentical hematopoietic stem cell transplantation. Best Pract Res Clin Haematol. 2011;24(3):339–349.
   PubMed Web of Science ®Google Scholar
• Bartelink IH, Belitser SV, Knibbe CA, et al. Immune reconstitution kinetics as an early predictor for mortality using various hematopoietic stem cell sources in children. Biol Blood Marrow Transplant. 2013;19(2):305–313.
   PubMed Web of Science ®Google Scholar
• Storek J, Gooley T, Witherspoon RP, et al. Infectious morbidity in long-term survivors of allogeneic marrow transplantation is associated with low CD4 T cell counts. Am J Hematol. 1997;54(2):131–138.
   PubMed Web of Science ®Google Scholar
• Clave E, Lisini D, Douay C, et al. Thymic function recovery after unrelated donor cord blood or T-cell depleted HLA-haploidentical stem cell transplantation correlates with leukemia relapse. Front Immunol. 2013;4:54.
   PubMed Web of Science ®Google Scholar
• Locatelli F, Giorgiani G, Di-Cesare-Merlone A, et al. The changing role of stem cell transplantation in childhood. Bone Marrow Transplant. 2008;41(Suppl 2):S37.
   Web of Science ®Google Scholar
• Mackall CL, Gress RE. Pathways of T-cell regeneration in mice and humans: implications for bone marrow transplantation and immunotherapy. Immunol Rev. 1997;157:61–72.
   PubMed Web of Science ®Google Scholar
• Sallusto F, Lenig D, Forster R, et al. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature. 1999;401(6754):708–712.
   PubMed Web of Science ®Google Scholar
• Douek DC, Vescio RA, Betts MR, et al. Assessment of thymic output in adults after haematopoietic stem-cell transplantation and prediction of T-cell reconstitution. Lancet. 2000;355(9218):1875–1881.
   PubMed Web of Science ®Google Scholar
• Haynes BF, Markert ML, Sempowski GD, et al. The role of the thymus in immune reconstitution in aging, bone marrow transplantation, and HIV-1 infection. Annu Rev Immunol. 2000;18:529–560.
   PubMed Web of Science ®Google Scholar
• Hakim FT, Cepeda R, Kaimei S, et al. Constraints on CD4 recovery postchemotherapy in adults: thymic insufficiency and apoptotic decline of expanded peripheral CD4 cells. Blood. 1997;90(9):3789–3798.
   PubMed Web of Science ®Google Scholar
• Eyrich M, Lang P, Lal S, et al. A prospective analysis of the pattern of immune reconstitution in a paediatric cohort following transplantation of positively selected human leucocyte antigen-disparate haematopoietic stem cells from parental donors. Br J Haematol. 2001;114(2):422–432.
   PubMed Web of Science ®Google Scholar
• Takahama Y. Journey through the thymus: stromal guides for T-cell development and selection. Nat Rev Immunol. 2006;6(2):127–135.
   PubMed Web of Science ®Google Scholar
• Velardi E, Dudakov JA, Van Den Brink MR. Clinical strategies to enhance thymic recovery after allogeneic hematopoietic stem cell transplantation. Immunol Lett. 2013;155(12):31–35.
   PubMed Web of Science ®Google Scholar
• Six EM, Benjelloun F, Garrigue A, et al. Cytokines and culture medium have a major impact on human in vitro T-cell differentiation. Blood Cells Mol Dis. 2011;47(1):72–78.
   PubMed Web of Science ®Google Scholar
• Reimann C, Six E, Dal-Cortivo L, et al. Human T-lymphoid progenitors generated in a feeder-cell-free Delta-like-4 culture system promote T-cell reconstitution in NOD/SCID/gammac(-/-) mice. Stem Cells. 2012;30(8):1771–1780.
   PubMed Web of Science ®Google Scholar
• Dudakov JA, Hanash AM, Jenq RR, et al. Interleukin-22 drives endogenous thymic regeneration in mice. Science. 2012;336(6077):91–95.
   PubMed Web of Science ®Google Scholar
• Sutherland JS, Goldberg GL, Hammett MV, et al. Activation of thymic regeneration in mice and humans following androgen blockade. J Immunol. 2005;175(4):2741–2753.
   PubMed Web of Science ®Google Scholar
• Hince M, Sakkal S, Vlahos K, et al. The role of sex steroids and gonadectomy in the control of thymic involution. Cell Immunol. 2008;252(12):122–138.
   PubMed Web of Science ®Google Scholar
• Finch PW, Rubin JS. Keratinocyte growth factor/fibroblast growth factor 7, a homeostatic factor with therapeutic potential for epithelial protection and repair. Adv Cancer Res. 2004;91:69–136.
   PubMed Web of Science ®Google Scholar
• Alpdogan O, Van Den Brink MR. IL-7 and IL-15: therapeutic cytokines for immunodeficiency. Trends Immunol. 2005;26(1):56–64.
   PubMed Web of Science ®Google Scholar
• Grabstein KH, Waldschmidt TJ, Finkelman FD, et al. Inhibition of murine B and T lymphopoiesis in vivo by an anti-interleukin 7 monoclonal antibody. J Exp Med. 1993;178(1):257–264.
   PubMed Web of Science ®Google Scholar
• Srinivasan A, Kasow KA, Cross S, et al. Phase I study of the tolerability and pharmacokinetics of palifermin in children undergoing allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2012;18(8):1309–1314.
   PubMed Web of Science ®Google Scholar
• Wang Y, Chen GH, Dp W, et al. Establishment of murine allogeneic umbilical cord blood cell transplantation model and study on the mechanism of keratinocyte growth factor enhancing immune reconstitution after transplantation. Zhonghua Xue Ye Xue Za Zhi. 2010;31(2):82–87.
   PubMedGoogle Scholar
• Wils EJ, Aerts-Kaya FS, Rombouts EJ, et al. Keratinocyte growth factor and stem cell factor to improve thymopoiesis after autologous CD34+ cell transplantation in rhesus macaques. Biol Blood Marrow Transplant. 2012;18(1):55–65.
   PubMed Web of Science ®Google Scholar
• Goldberg JD, Zheng J, Castro-Malaspina H, et al. Palifermin is efficacious in recipients of TBI-based but not chemotherapy-based allogeneic hematopoietic stem cell transplants. Bone Marrow Transplant. 2013;48(1):99–104.
   PubMed Web of Science ®Google Scholar
• Puel A, Ziegler SF, Buckley RH, et al. Defective IL7R expression in T(-)B(+)NK(+) severe combined immunodeficiency. Nat Genet. 1998;20(4):394–397.
   PubMed Web of Science ®Google Scholar
• Sportes C, Babb RR, Krumlauf MC, et al. Phase I study of recombinant human interleukin-7 administration in subjects with refractory malignancy. Clin Cancer Res. 2010;16(2):727–735.
   PubMed Web of Science ®Google Scholar
• Velardi E, Dudakov JA, Van Den Brink MR. Sex steroid ablation: an immunoregenerative strategy for immunocompromised patients. Bone Marrow Transplant. 2015;50(Suppl 2):S7781.
   Google Scholar
• Dudakov JA, Goldberg GL, Reiseger JJ, et al. Withdrawal of sex steroids reverses age- and chemotherapy-related defects in bone marrow lymphopoiesis. J Immunol. 2009;182(10):6247–6260.
   PubMed Web of Science ®Google Scholar
• Yun HD, Waller EK. Finding the sweet spot for donor lymphocyte infusions. Biol Blood Marrow Transplant. 2013;19(4):507–508.
   PubMed Web of Science ®Google Scholar
• Kolb HJ, Mittermuller J, Clemm C, et al. Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. Blood. 1990;76(12):2462–2465.
   PubMed Web of Science ®Google Scholar
• Simula MP, Marktel S, Fozza C, et al. Response to donor lymphocyte infusions for chronic myeloid leukemia is dose-dependent: the importance of escalating the cell dose to maximize therapeutic efficacy. Leukemia. 2007;21(5):943–948.
   PubMed Web of Science ®Google Scholar
• Yoshimi A, Bader P, Matthes-Martin S, et al. Donor leukocyte infusion after hematopoietic stem cell transplantation in patients with juvenile myelomonocytic leukemia. Leukemia. 2005;19(6):971–977.
   PubMed Web of Science ®Google Scholar
• Atra A, Millar B, Shepherd V, et al. Donor lymphocyte infusion for childhood acute lymphoblastic leukaemia relapsing after bone marrow transplantation. Br J Haematol. 1997;97(1):165–168.
   PubMed Web of Science ®Google Scholar
• De Rosa G, Pezzullo L, Scarpato N, et al. Donor lymphocyte infusion for post-transplant relapse of Hodgkin’s lymphoma. Haematologica. 2000;85(7):780–781.
   PubMed Web of Science ®Google Scholar
• Bloor AJ, Thomson K, Chowdhry N, et al. High response rate to donor lymphocyte infusion after allogeneic stem cell transplantation for indolent non-Hodgkin lymphoma. Biol Blood Marrow Transplant. 2008;14(1):50–58.
   PubMed Web of Science ®Google Scholar
• Alyea E, Weller E, Schlossman R, et al. T-cell–depleted allogeneic bone marrow transplantation followed by donor lymphocyte infusion in patients with multiple myeloma: induction of graft-versus-myeloma effect. Blood. 2001;98(4):934–939.
   PubMed Web of Science ®Google Scholar
• Fozza C, Szydlo RM, Abdel-Rehim MM, et al. Factors for graft-versus-host disease after donor lymphocyte infusions with an escalating dose regimen: lack of association with cell dose. Br J Haematol. 2007;136(6):833–836.
   PubMed Web of Science ®Google Scholar
• Guglielmi C, Arcese W, Dazzi F, et al. Donor lymphocyte infusion for relapsed chronic myelogenous leukemia: prognostic relevance of the initial cell dose. Blood. 2002;100(2):397–405.
   PubMed Web of Science ®Google Scholar
• Schaap N, Schattenberg A, Bar B, et al. Induction of graft-versus-leukemia to prevent relapse after partially lymphocyte-depleted allogeneic bone marrow transplantation by pre-emptive donor leukocyte infusions. Leukemia. 2001;15(9):1339–1346.
   PubMed Web of Science ®Google Scholar
• Barrett AJ, Mavroudis D, Tisdale J, et al. T cell-depleted bone marrow transplantation and delayed T cell add-back to control acute GVHD and conserve a graft-versus-leukemia effect. Bone Marrow Transplant. 1998;21(6):543–551.
   PubMed Web of Science ®Google Scholar
• Ferra C, Rodriguez-Luaces M, Gallardo D, et al. Individually adjusted prophylactic donor lymphocyte infusions after CD34-selected allogeneic peripheral blood stem cell transplantation. Bone Marrow Transplant. 2001;28(10):963–968.
   PubMed Web of Science ®Google Scholar
• Lee SJ, Klein JP, Barrett AJ, et al. Severity of chronic graft-versus-host disease: association with treatment-related mortality and relapse. Blood. 2002;100(2):406–414.
   PubMed Web of Science ®Google Scholar
• Lee CK, De Magalhaes-Silverman M, Hohl RJ, et al. Prophylactic T cell infusion after T cell-depleted bone marrow transplantation in patients with refractory lymphoma. Bone Marrow Transplant. 2002;29(7):615–620.
   PubMed Web of Science ®Google Scholar
• Montero A, Savani BN, Shenoy A, et al. T-cell depleted peripheral blood stem cell allotransplantation with T-cell add-back for patients with hematological malignancies: effect of chronic GVHD on outcome. Biol Blood Marrow Transplant. 2006;12(12):1318–1325.
   PubMed Web of Science ®Google Scholar
• De Lima M, Bonamino M, Vasconcelos Z, et al. Prophylactic donor lymphocyte infusions after moderately ablative chemotherapy and stem cell transplantation for hematological malignancies: high remission rate among poor prognosis patients at the expense of graft-versus-host disease. Bone Marrow Transplant. 2001;27(1):73–78.
   PubMed Web of Science ®Google Scholar
• Dodero A, Carniti C, Raganato A, et al. Haploidentical stem cell transplantation after a reduced-intensity conditioning regimen for the treatment of advanced hematologic malignancies: posttransplantation CD8-depleted donor lymphocyte infusions contribute to improve T-cell recovery. Blood. 2009;113(19):4771–4779.
   PubMed Web of Science ®Google Scholar
• Meyer RG, Britten CM, Wehler D, et al. Prophylactic transfer of CD8-depleted donor lymphocytes after T-cell-depleted reduced-intensity transplantation. Blood. 2007;109(1):374–382.
   PubMed Web of Science ®Google Scholar
• Shimoni A, Gajewski JA, Donato 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(10):568–575.
   PubMed Web of Science ®Google Scholar
• Champlin R, Ho W, Gajewski J, et al. Selective depletion of CD8+ T lymphocytes for prevention of graft-versus-host disease after allogeneic bone marrow transplantation. Blood. 1990;76(2):418–423.
   PubMed Web of Science ®Google Scholar
• Nagler A, Condiotti R, Nabet C, et al. Selective CD4+ T-cell depletion does not prevent graft-versus-host disease. Transplantation. 1998;66(1):138–141.
   PubMed Web of Science ®Google Scholar
• Amrolia PJ, 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(6):1797–1808.
   PubMed Web of Science ®Google Scholar
• 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(9327):130–137.
   PubMed Web of Science ®Google Scholar
• Perruccio K, Topini F, Tosti A, et al. Optimizing a photoallodepletion protocol for adoptive immunotherapy after haploidentical SCT. Bone Marrow Transplant. 2012;47(9):1196–1200.
   PubMed Web of Science ®Google Scholar
• Perruccio K, Topini F, Tosti A, et al. Photodynamic purging of alloreactive T cells for adoptive immunotherapy after haploidentical stem cell transplantation. Blood Cells Mol Dis. 2008;40(1):76–83.
   PubMed Web of Science ®Google Scholar
• Durakovic N, Radojcic V, Powell J, et al. Rapamycin promotes emergence of IL-10-secreting donor lymphocyte infusion-derived T cells without compromising their graft-versus-leukemia reactivity. Transplantation. 2007;83(5):631–640.
   PubMed Web of Science ®Google Scholar
• Maury S, Lemoine FM, Hicheri Y, et al. CD4+CD25+ regulatory T cell depletion improves the graft-versus-tumor effect of donor lymphocytes after allogeneic hematopoietic stem cell transplantation. Sci Transl Med. 2010;2(41):41ra52.
   PubMed Web of Science ®Google Scholar
• Hardy NM, Fellowes V, Rose JJ, et al. Costimulated tumor-infiltrating lymphocytes are a feasible and safe alternative donor cell therapy for relapse after allogeneic stem cell transplantation. Blood. 2012;119(12):2956–2959.
   PubMed Web of Science ®Google Scholar
• Porter DL, Levine BL, Bunin N, et al. A phase 1 trial of donor lymphocyte infusions expanded and activated ex vivo via CD3/CD28 costimulation. Blood. 2006;107(4):1325–1331.
   PubMed Web of Science ®Google Scholar
• Slavin S, Naparstek E, Nagler A, et al. Allogeneic cell therapy with donor peripheral blood cells and recombinant human interleukin-2 to treat leukemia relapse after allogeneic bone marrow transplantation. Blood. 1996;87(6):2195–2204.
   PubMed Web of Science ®Google Scholar
• Nadal E, Fowler A, Kanfer E, et al. Adjuvant interleukin-2 therapy for patients refractory to donor lymphocyte infusions. Exp Hematol. 2004;32(2):218–223.
   PubMed Web of Science ®Google Scholar
• Theurich S, Malcher J, Wennhold K, et al. Brentuximab vedotin combined with donor lymphocyte infusions for early relapse of Hodgkin lymphoma after allogeneic stem-cell transplantation induces tumor-specific immunity and sustained clinical remission. J Clin Oncol. 2013;31(5):e59e63.
   Web of Science ®Google Scholar
• Berglund S, Gertow J, Uhlin M, et al. Expanded umbilical cord blood T cells used as donor lymphocyte infusions after umbilical cord blood transplantation. Cytotherapy. 2014;16(11):1528–1536.
   PubMed Web of Science ®Google Scholar
• Lindemans CA, Chiesa R, Amrolia PJ, et al. Impact of thymoglobulin prior to pediatric unrelated umbilical cord blood transplantation on immune reconstitution and clinical outcome. Blood. 2014;123(1):126–132.
   PubMed Web of Science ®Google Scholar
• Teschner D, Distler E, Wehler D, et al. Depletion of naive T cells using clinical grade magnetic CD45RA beads: a new approach for GVHD prophylaxis. Bone Marrow Transplant. 2014;49(1):138–144.
   PubMed Web of Science ®Google Scholar
• Bleakley M, Heimfeld S, Loeb KR, et al. Outcomes of acute leukemia patients transplanted with naive T cell-depleted stem cell grafts. J Clin Invest. 2015;125(7):2677–2689.
   PubMed Web of Science ®Google Scholar
• Ciceri F, Bonini C, Gallo-Stampino C, et al. Modulation of GvHD by suicide-gene transduced donor T lymphocytes: clinical applications in mismatched transplantation. Cytotherapy. 2005;7(2):144–149.
   PubMed Web of Science ®Google Scholar
• Bonini C, Ferrari G, Verzeletti S, et al. HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia. Science. 1997;276(5319):1719–1724.
   PubMed Web of Science ®Google Scholar
• Ciceri F, Bonini C, Marktel S, et al. Antitumor effects of HSV-TK-engineered donor lymphocytes after allogeneic stem-cell transplantation. Blood. 2007;109(11):4698–4707.
   PubMed Web of Science ®Google Scholar
• Ciceri F, Bonini C, Stanghellini MT, et al. Infusion of suicide-gene-engineered donor lymphocytes after family haploidentical haemopoietic stem-cell transplantation for leukaemia (the TK007 trial): a non-randomised phase I-II study. Lancet Oncol. 2009;10(5):489–500.
   PubMed Web of Science ®Google Scholar
• Di Stasi A, Tey SK, Dotti G, et al. Inducible apoptosis as a safety switch for adoptive cell therapy. N Engl J Med. 2011;365(18):1673–1683.
   PubMed Web of Science ®Google Scholar
• Zhou X, Di Stasi A, Tey SK, et al. Long-term outcome after haploidentical stem cell transplant and infusion of T cells expressing the inducible caspase 9 safety transgene. Blood. 2014;123(25):3895–3905.
   PubMed Web of Science ®Google Scholar
• Zhou X, Dotti G, Krance RA, et al. Inducible caspase-9 suicide gene controls adverse effects from alloreplete T cells after haploidentical stem cell transplantation. Blood. 2015;125(26):4103–4113.
   PubMed Web of Science ®Google Scholar
• Traversari C, Marktel S, Magnani Z, et al. The potential immunogenicity of the TK suicide gene does not prevent full clinical benefit associated with the use of TK-transduced donor lymphocytes in HSCT for hematologic malignancies. Blood. 2007;109(11):4708–4715.
   PubMed Web of Science ®Google Scholar
• Chaleff S, Otto M, Barfield RC, et al. A large-scale method for the selective depletion of alphabeta T lymphocytes from PBSC for allogeneic transplantation. Cytotherapy. 2007;9(8):746–754.
   PubMed Web of Science ®Google Scholar
• Bertaina A, Merli P, Rutella S, et al. HLA-haploidentical stem cell transplantation after removal of alphabeta+ T and B cells in children with nonmalignant disorders. Blood. 2014;124(5):822–826.
   PubMed Web of Science ®Google Scholar
• Airoldi I, Bertaina A, Prigione I, et al. gammadelta T-cell reconstitution after HLA-haploidentical hematopoietic transplantation depleted of TCR-alphabeta+/CD19+ lymphocytes. Blood. 2015;125(15):2349–2358.
   PubMed Web of Science ®Google Scholar
• Riddell SR, Watanabe KS, Goodrich JM, et al. Restoration of viral immunity in immunodeficient humans by the adoptive transfer of T cell clones. Science. 1992;257(5067):238–241.
   PubMed Web of Science ®Google Scholar
• Walter EA, Greenberg PD, Gilbert MJ, 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(16):1038–1044.
   PubMed Web of Science ®Google Scholar
• Einsele H, Roosnek E, Rufer N, et al. Infusion of cytomegalovirus (CMV)-specific T cells for the treatment of CMV infection not responding to antiviral chemotherapy. Blood. 2002;99(11):3916–3922.
   PubMed Web of Science ®Google Scholar
• Rooney CM, Smith CA, Ng CY, et al. Use of gene-modified virus-specific T lymphocytes to control Epstein-Barr-virus-related lymphoproliferation. Lancet. 1995;345(8941):9–13.
   PubMed Web of Science ®Google Scholar
• Comoli P, Basso S, Labirio M, et al. T cell therapy of Epstein-Barr virus and adenovirus infections after hemopoietic stem cell transplant. Blood Cells Mol Dis. 2008;40(1):68–70.
   PubMed Web of Science ®Google Scholar
• Melenhorst JJ, Leen AM, Bollard CM, et al. Allogeneic virus-specific T cells with HLA alloreactivity do not produce GVHD in human subjects. Blood. 2010;116(22):4700–4702.
   PubMed Web of Science ®Google Scholar
• Peggs KS, Verfuerth S, Pizzey A, et al. Adoptive cellular therapy for early cytomegalovirus infection after allogeneic stem-cell transplantation with virus-specific T-cell lines. Lancet. 2003;362(9393):1375–1377.
   PubMed Web of Science ®Google Scholar
• Manz R, Assenmacher M, Pfluger E, et al. Analysis and sorting of live cells according to secreted molecules, relocated to a cell-surface affinity matrix. Proc Natl Acad Sci U S A. 1995;92(6):1921–1925.
   PubMed Web of Science ®Google Scholar
• Cobbold M, Khan N, Pourgheysari B, et al. Adoptive transfer of cytomegalovirus-specific CTL to stem cell transplant patients after selection by HLA-peptide tetramers. J Exp Med. 2005;202(3):379–386.
   PubMed Web of Science ®Google Scholar
• Odendahl M, Grigoleit GU, Bonig H, et al. Clinical-scale isolation of ‘minimally manipulated’ cytomegalovirus-specific donor lymphocytes for the treatment of refractory cytomegalovirus disease. Cytotherapy. 2014;16(9):1245–1256.
   PubMed Web of Science ®Google Scholar
• Feuchtinger T, Matthes-Martin S, Richard C, 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(1):64–76.
   PubMed Web of Science ®Google Scholar
• Perruccio K, Tosti A, Burchielli E, et al. Transferring functional immune responses to pathogens after haploidentical hematopoietic transplantation. Blood. 2005;106(13):4397–4406.
   PubMed Web of Science ®Google Scholar
• Hanley PJ, Cruz CR, Savoldo B, et al. Functionally active virus-specific T cells that target CMV, adenovirus, and EBV can be expanded from naive T-cell populations in cord blood and will target a range of viral epitopes. Blood. 2009;114(9):1958–1967.
   PubMed Web of Science ®Google Scholar
• Comoli P, Ginevri F, Maccario R, et al. Successful in vitro priming of EBV-specific CD8+ T cells endowed with strong cytotoxic function from T cells of EBV-seronegative children. Am J Transplant. 2006;6(9):2169–2176.
   PubMed Web of Science ®Google Scholar
• Leen AM, Myers GD, Sili U, et al. Monoculture-derived T lymphocytes specific for multiple viruses expand and produce clinically relevant effects in immunocompromised individuals. Nat Med. 2006;12(10):1160–1166.
   PubMed Web of Science ®Google Scholar
• Gerdemann U, Christin AS, Vera JF, et al. Nucleofection of DCs to generate Multivirus-specific T cells for prevention or treatment of viral infections in the immunocompromised host. Mol Ther. 2009;17(9):1616–1625.
   PubMed Web of Science ®Google Scholar
• Gerdemann U, Katari UL, Papadopoulou A, et al. Safety and clinical efficacy of rapidly-generated trivirus-directed T cells as treatment for adenovirus, EBV, and CMV infections after allogeneic hematopoietic stem cell transplant. Mol Ther. 2013;21(11):2113–2121.
   PubMed Web of Science ®Google Scholar
• Vera JF, Brenner LJ, Gerdemann U, et al. Accelerated production of antigen-specific T cells for preclinical and clinical applications using gas-permeable rapid expansion cultureware (G-Rex). J Immunother. 2010;33(3):305–315.
   PubMed Web of Science ®Google Scholar
• Papadopoulou A, Gerdemann U, Katari UL, et al. Activity of broad-spectrum T cells as treatment for AdV, EBV, CMV, BKV, and HHV6 infections after HSCT. Sci Transl Med. 2014;6(242):242ra83.
   PubMed Web of Science ®Google Scholar
• Haque T, Wilkie GM, Taylor C, et al. Treatment of Epstein-Barr-virus-positive post-transplantation lymphoproliferative disease with partly HLA-matched allogeneic cytotoxic T cells. Lancet. 2002;360(9331):436–442.
   PubMed Web of Science ®Google Scholar
• Leen AM, Bollard CM, Mendizabal AM, et al. Multicenter study of banked third-party virus-specific T cells to treat severe viral infections after hematopoietic stem cell transplantation. Blood. 2013;121(26):5113–5123.
   PubMed Web of Science ®Google Scholar
• Knabel M, Franz TJ, Schiemann M, et al. Reversible MHC multimer staining for functional isolation of T-cell populations and effective adoptive transfer. Nat Med. 2002;8(6):631–637.
   PubMed Web of Science ®Google Scholar
• Schmitt A, Tonn T, Busch DH, et al. Adoptive transfer and selective reconstitution of streptamer-selected cytomegalovirus-specific CD8+ T cells leads to virus clearance in patients after allogeneic peripheral blood stem cell transplantation. Transfusion. 2011;51(3):591–599.
   PubMed Web of Science ®Google Scholar
• Uhlin M, Okas M, Gertow J, et al. A novel haplo-identical adoptive CTL therapy as a treatment for EBV-associated lymphoma after stem cell transplantation. Cancer Immunol Immunother. 2010;59(3):473–477.
   PubMed Web of Science ®Google Scholar
• Freimuller C, Stemberger J, Artwohl M, et al. Selection of adenovirus-specific and Epstein-Barr virus-specific T cells with major histocompatibility class I streptamers under Good Manufacturing Practice (GMP)-compliant conditions. Cytotherapy. 2015;17(7):989–1007.
   PubMed Web of Science ®Google Scholar
• Feuchtinger T, Lang P, Hamprecht K, et al. Isolation and expansion of human adenovirus-specific CD4+ and CD8+ T cells according to IFN-gamma secretion for adjuvant immunotherapy. Exp Hematol. 2004;32(3):282–289.
   PubMed Web of Science ®Google Scholar
• Di Nardo M, Li Pira G, Amodeo A, et al. Adoptive immunotherapy with antigen-specific T cells during extracorporeal membrane oxygenation (ECMO) for adenovirus-related respiratory failure in a child given haploidentical stem cell transplantation. Pediatr Blood Cancer. 2014;61(2):376–379.
   PubMed Web of Science ®Google Scholar
• Feuchtinger T, Opherk K, Bethge WA, et al. Adoptive transfer of pp65-specific T cells for the treatment of chemorefractory cytomegalovirus disease or reactivation after haploidentical and matched unrelated stem cell transplantation. Blood. 2010;116(20):4360–4367.
   PubMed Web of Science ®Google Scholar
• Fischer K, Voelkl S, Heymann J, et al. Isolation and characterization of human antigen-specific TCR alpha beta+ CD4(-)CD8- double-negative regulatory T cells. Blood. 2005;105(7):2828–2835.
   PubMed Web of Science ®Google Scholar
• Filaci G, Suciu-Foca N. CD8+ T suppressor cells are back to the game: are they players in autoimmunity? Autoimmun Rev. 2002;1(5):279–283.
   PubMedGoogle Scholar
• Allan SE, Broady R, Gregori S, et al. CD4+ T-regulatory cells: toward therapy for human diseases. Immunol Rev. 2008;223:391–421.
   PubMed Web of Science ®Google Scholar
• Abbas AK, Benoist C, Bluestone JA, et al. Regulatory T cells: recommendations to simplify the nomenclature. Nat Immunol. 2013;14(4):307–308.
   PubMed Web of Science ®Google Scholar
• Sakaguchi S. Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat Immunol. 2005;6(4):345–352.
   PubMed Web of Science ®Google Scholar
• Liu W, Putnam AL, Xu-Yu Z, et al. CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells. J Exp Med. 2006;203(7):1701–1711.
   PubMed Web of Science ®Google Scholar
• Seddiki N, Santner-Nanan B, Martinson J, et al. Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells. J Exp Med. 2006;203(7):1693–1700.
   PubMed Web of Science ®Google Scholar
• Levings MK, Roncarolo MG. Phenotypic and functional differences between human CD4+CD25+ and type 1 regulatory T cells. Curr Top Microbiol Immunol. 2005;293:303–326.
   PubMed Web of Science ®Google Scholar
• Bacchetta R, Passerini L, Gambineri E, et al. Defective regulatory and effector T cell functions in patients with FOXP3 mutations. J Clin Invest. 2006;116(6):1713–1722.
   PubMed Web of Science ®Google Scholar
• Passerini L, Di Nunzio S, Gregori S, et al. Functional type 1 regulatory T cells develop regardless of FOXP3 mutations in patients with IPEX syndrome. Eur J Immunol. 2011;41(4):1120–1131.
   PubMed Web of Science ®Google Scholar
• Levings MK, Sangregorio R, Roncarolo MG. Human cd25(+)cd4(+) t regulatory cells suppress naive and memory T cell proliferation and can be expanded in vitro without loss of function. J Exp Med. 2001;193(11):1295–1302.
   PubMed Web of Science ®Google Scholar
• Jonuleit H, Schmitt E, Stassen M, et al. Identification and functional characterization of human CD4(+)CD25(+) T cells with regulatory properties isolated from peripheral blood. J Exp Med. 2001;193(11):1285–1294.
   PubMed Web of Science ®Google Scholar
• Baron U, Floess S, Wieczorek G, et al. DNA demethylation in the human FOXP3 locus discriminates regulatory T cells from activated FOXP3(+) conventional T cells. Eur J Immunol. 2007;37(9):2378–2389.
   PubMed Web of Science ®Google Scholar
• Floess S, Freyer J, Siewert C, et al. Epigenetic control of the foxp3 locus in regulatory T cells. PLoS Biol. 2007;5(2):e38.
   PubMed Web of Science ®Google Scholar
• Sehouli J, Loddenkemper C, Cornu T, et al. Epigenetic quantification of tumor-infiltrating T-lymphocytes. Epigenetics. 2011;6:2.
   Web of Science ®Google Scholar
• Hoffmann P, Boeld TJ, Eder R, et al. Isolation of CD4+CD25+ regulatory T cells for clinical trials. Biol Blood Marrow Transplant. 2006;12(3):267–274.
   PubMed Web of Science ®Google Scholar
• Brunstein CG, Miller JS, Cao Q, et al. Infusion of ex vivo expanded T regulatory cells in adults transplanted with umbilical cord blood: safety profile and detection kinetics. Blood. 2011;117(3):1061–1070.
   PubMed Web of Science ®Google Scholar
• Brunstein CG, Blazar BR, Miller JS, et al. Adoptive transfer of umbilical cord blood-derived regulatory T cells and early viral reactivation. Biol Blood Marrow Transplant. 2013;19(8):1271–1273.
   PubMed Web of Science ®Google Scholar
• Di Ianni M, Falzetti F, Carotti A, et al. Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation. Blood. 2011;117(14):3921–3928.
   PubMed Web of Science ®Google Scholar
• Martelli MF, Di Ianni M, Ruggeri L, et al. HLA-haploidentical transplantation with regulatory and conventional T-cell adoptive immunotherapy prevents acute leukemia relapse. Blood. 2014;124(4):638–644.
   PubMed Web of Science ®Google Scholar
• Di Ianni M, Falzetti F, Carotti A, et al. Immunoselection and clinical use of T regulatory cells in HLA-haploidentical stem cell transplantation. Best Pract Res Clin Haematol. 2011;24(3):459–466.
   PubMed Web of Science ®Google Scholar
• Parmar S, Liu X, Najjar A, et al. Ex vivo fucosylation of third-party human regulatory T cells enhances anti-graft-versus-host disease potency in vivo. Blood. 2015;125(9):1502–1506.
   PubMed Web of Science ®Google Scholar
• Schneidawind D, Baker J, Pierini A, et al. Third-party CD4+ invariant natural killer T cells protect from murine GVHD lethality. Blood. 2015;125(22):3491–3500.
   PubMed Web of Science ®Google Scholar
• Schneidawind D, Pierini A, Alvarez M, et al. CD4+ invariant natural killer T cells protect from murine GVHD lethality through expansion of donor CD4+CD25+FoxP3+ regulatory T cells. Blood. 2014;124(22):3320–3328.
   PubMed Web of Science ®Google Scholar
• Battaglia M, Stabilini A, Migliavacca B, et al. Rapamycin promotes expansion of functional CD4+CD25+FOXP3+ regulatory T cells of both healthy subjects and type 1 diabetic patients. J Immunol. 2006;177(12):8338–8347.
   PubMed Web of Science ®Google Scholar
• Battaglia M, Stabilini A, Roncarolo MG. Rapamycin selectively expands CD4+CD25+FoxP3+ regulatory T cells. Blood. 2005;105(12):4743–4748.
   PubMed Web of Science ®Google Scholar
• Monti P, Scirpoli M, Maffi P, et al. Rapamycin monotherapy in patients with type 1 diabetes modifies CD4+CD25+FOXP3+ regulatory T-cells. Diabetes. 2008;57(9):2341–2347.
   PubMed Web of Science ®Google Scholar
• Peccatori J, Forcina A, Clerici D, et al. Sirolimus-based graft-versus-host disease prophylaxis promotes the in vivo expansion of regulatory T cells and permits peripheral blood stem cell transplantation from haploidentical donors. Leukemia. 2015;29(2):396–405.
   PubMed Web of Science ®Google Scholar
• Kanakry CG, Ganguly S, Zahurak M, et al. Aldehyde dehydrogenase expression drives human regulatory T cell resistance to posttransplantation cyclophosphamide. Sci Transl Med. 2013;5(211):211ra157.
   PubMed Web of Science ®Google Scholar
• Cieri N, Greco R, Crucitti L, et al. Post-transplant Cyclophosphamide and Sirolimus after Haploidentical HSCT Using a Treosulfan-based myeloablative conditioning and PBSC. Biol Blood Marrow Transplant. 2015;21(8):1506–1514.
   PubMed Web of Science ®Google Scholar
• Gregori S, Tomasoni D, Pacciani V, et al. Differentiation of type 1 T regulatory cells (Tr1) by tolerogenic DC-10 requires the IL-10-dependent ILT4/HLA-G pathway. Blood. 2010;116(6):935–944.
   PubMed Web of Science ®Google Scholar
• Bacchetta R, Gregori S, Serafini G, et al. Molecular and functional characterization of allogantigen-specific anergic T cells suitable for cell therapy. Haematologica. 2010;95(12):2134–2143.
   PubMed Web of Science ®Google Scholar
• Gill S, June CH. Going viral: chimeric antigen receptor T-cell therapy for hematological malignancies. Immunol Rev. 2015;263(1):68–89.
   PubMed Web of Science ®Google Scholar