Preventing stem cell transplantation-associated viral infections using T-cell therapy

Immunotherapy

Volumn 7, Issue 7, 2015, Pages 793-810

  Tzannou, Ifigeneia ^a   Leen, Ann M ^a  

^a TEXAS CHILDREN S HOSPITAL   (United States)

Author keywords

adoptive immunotherapy; hematopoietic stem cell transplantation; T cells; viral infections

Indexed keywords

GAMMA INTERFERON; POLYMER;

CELL EXPANSION; CELL ISOLATION; CELL THERAPY; CYTOMEGALOVIRUS; DNA MODIFICATION; DONOR LYMPHOCYTE INFUSION; EPSTEIN BARR VIRUS; EX VIVO ALLODEPLETION; HUMAN; IMMUNOTHERAPY; NONHUMAN; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; REVIEW; STEM CELL TRANSPLANTATION; SUICIDE GENE; T CELL DEPLETION; T CELL THERAPY; VIRUS INFECTION; ALLOGRAFT; GENETIC DISEASES, INBORN; HEMATOLOGIC NEOPLASMS; HEMATOPOIETIC STEM CELL TRANSPLANTATION; IMMUNOLOGY; PROCEDURES; T LYMPHOCYTE; TRANSPLANTATION; VIRUS DISEASES;

ALLOGRAFTS; GENETIC DISEASES, INBORN; HEMATOLOGIC NEOPLASMS; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMANS; IMMUNOTHERAPY; T-LYMPHOCYTES; VIRUS DISEASES;

EID: 84942079728     PISSN: 1750743X     EISSN: 17507448     Source Type: Journal    
DOI: 10.2217/imt.15.43     Document Type: Review

References (110)

1. Gaziev J, Lucarelli G. Stem cell transplantation and gene therapy for hemoglobinopathies. Curr. Hematol. Rep. 4(2), 126-131 (2005).
2. Gupta V, Tallman MS, Weisdorf DJ. Allogeneic hematopoietic cell transplantation for adults with acute myeloid leukemia: myths, controversies, and unknowns. Blood 117(8), 2307-2318 (2011).
3. Peffault de Latour R, Porcher R, Dalle JH et al. Allogeneic hematopoietic stem cell transplantation in Fanconi anemia: the European Group for Blood and Marrow Transplantation experience. Blood 122(26), 4279-4286 (2013).
4. Samarasinghe S, Steward C, Hiwarkar P et al. Excellent outcome of matched unrelated donor transplantation in paediatric aplastic anaemia following failure with immunosuppressive therapy: A United Kingdom multicentre retrospective experience. Br. J. Haematol. 157(3), 339-346 (2012).
5. Saussele S, Hehlmann R, Gratwohl A, Hochhaus A. Outcome of patients with CML after SCT in the era of tyrosine kinase inhibitors. Bone Marrow Transplant. 47(2), 304 (2012).
6. Gratwohl A, Brand R, Frassoni F et al. Cause of death after allogeneic haematopoietic stem cell transplantation (HSCT) in early leukaemias: An EBMT analysis of lethal infectious complications and changes over calendar time. Bone Marrow Transplant. 36(9), 757-769 (2005).
7. Bacigalupo A, Soraru M, Dominietto A et al. Allogeneic hemopoietic SCT for patients with primary myelofibrosis: A predictive transplant score based on transfusion requirement, spleen size and donor type. Bone Marrow Transplant. 45(3), 458-463 (2010).
8. Locatelli F, Crotta A, Ruggeri A et al. Analysis of risk factors influencing outcomes after cord blood transplantation in children with juvenile myelomonocytic leukemia: A EUROCORD, EBMT, EWOG-MDS, CIBMTR study. Blood 122(12), 2135-2141 (2013).
9. Sangiolo D, Storb R, Deeg HJ et al. Outcome of allogeneic hematopoietic cell transplantation from HLA-identical siblings for severe aplastic anemia in patients over 40 years of age. Biol. Blood Marrow Transplant. 16(10), 1411-1418 (2010).
10. Ljungman P, Perez-Bercoff L, Jonsson J et al. Risk factors for the development of cytomegalovirus disease after allogeneic stem cell transplantation. Haematologica 91(1), 78-83 (2006).
11. Ljungman P, de la Camara R, Cordonnier C et al. Management of CMV, HHV-6, HHV-7 and Kaposi-sarcoma herpesvirus (HHV-8) infections in patients with hematological malignancies and after SCT. Bone Marrow Transplant. 42(4), 227-240 (2008).
12. Styczynski J, Reusser P, Einsele H et al. Management of HSV, VZV and EBV infections in patients with hematological malignancies and after SCT: guidelines from the Second European Conference on Infections in Leukemia. Bone Marrow Transplant. 43(10), 757-770 (2009).
13. de Pagter PJ, Schuurman R, Meijer E, van BD, Sanders EA, Boelens JJ. Human herpesvirus type 6 reactivation after haematopoietic stem cell transplantation. J. Clin. Virol. 43(4), 361-366 (2008).
14. Hubacek P, Sedlacek P, Keslova P et al. Incidence of HHV7 in donors and recipients of allogeneic hematopoietic stem cell transplantation. Pediatr. Blood Cancer 50(4), 935 (2008).
15. Comoli P, Hirsch HH, Ginevri F. Cellular immune responses to BK virus. Curr. Opin. Organ Transplant. 13(6), 569-574 (2008).
16. Koskenvuo M, Dumoulin A, Lautenschlager I et al. BK polyomavirus-associated hemorrhagic cystitis among pediatric allogeneic bone marrow transplant recipients: treatment response and evidence for nosocomial transmission. J. Clin. Virol. 56(1), 77-81 (2013).
17. Engelhard D, Mohty B, de la Camara R, Cordonnier C, Ljungman P. European guidelines for prevention and management of influenza in hematopoietic stem cell transplantation and leukemia patients: summary of ECIL-4 (2011), on behalf of ECIL, a joint venture of EBMT, EORTC, ICHS, and ELN. Transpl. Infect. Dis. 15(3), 219-232 (2013).
18. Hirsch HH, Martino R, Ward KN, Boeckh M, Einsele H, Ljungman P. Fourth European Conference on Infections in Leukaemia (ECIL-4): guidelines for diagnosis and treatment of human respiratory syncytial virus, parainfluenza virus, metapneumovirus, rhinovirus, and coronavirus. Clin. Infect. Dis. 56(2), 258-266 (2013).
19. Lo MS, Lee GM, Gunawardane N, Burchett SK, Lachenauer CS, Lehmann LE. The impact of RSV, adenovirus, influenza, and parainfluenza infection in pediatric patients receiving stem cell transplant, solid organ transplant, or cancer chemotherapy. Pediatr. Transplant. 17(2), 133-143 (2013).
20. Renaud C, Xie H, Seo S et al. Mortality rates of human metapneumovirus and respiratory syncytial virus lower respiratory tract infections in hematopoietic cell transplantation recipients. Biol. Blood Marrow Transplant. 19(8), 1220-1226 (2013).
21. Matthes-Martin S, Feuchtinger T, Shaw PJ et al. European guidelines for diagnosis and treatment of adenovirus infection in leukemia and stem cell transplantation: summary of ECIL-4 (2011). Transpl. Infect. Dis. 14(6), 555-563 (2012).
22. Marr KA. Delayed opportunistic infections in hematopoietic stem cell transplantation patients: A surmountable challenge. Hematology. Am. Soc. Hematol. Educ. Program 2012, 265-270 (2012).
23. Boeckh M, Erard V, Zerr D, Englund J. Emerging viral infections after hematopoietic cell transplantation. Pediatr. Transplant. 9(Suppl. 7), 48-54 (2005).
24. Tomblyn M, Chiller T, Einsele H et al. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: A global perspective. Biol. Blood Marrow Transplant. 15(10), 1143-1238 (2009).
25. Zaia J, Baden L, Boeckh MJ et al. Viral disease prevention after hematopoietic cell transplantation. Bone Marrow Transplant. 44(8), 471-482 (2009).
26. Papadopoulos EB, Ladanyi M, Emanuel D et al. Infusions of donor leukocytes to treat Epstein-Barr virus-associated lymphoproliferative disorders after allogeneic bone marrow transplantation. N. Engl. J. Med. 330(17), 1185-1191 (1994).
27. Hromas R, Cornetta K, Srour E, Blanke C, Broun ER. Donor leukocyte infusion as therapy of life-threatening adenoviral infections after T-cell-depleted bone marrow transplantation. Blood 84(5), 1689-1690 (1994).
28. Couriel D, Canosa J, Engler H, Collins A, Dunbar C, Barrett AJ. Early reactivation of cytomegalovirus and high risk of interstitial pneumonitis following T depleted BMT for adults with hematological malignancies. Bone Marrow Transplant. 18(2), 347-353 (1996).
29. Yoshihara S, Kato R, Inoue T et al. Successful treatment of life-threatening human herpesvirus-6 encephalitis with donor lymphocyte infusion in a patient who had undergone human leukocyte antigen-haploidentical nonmyeloablative stem cell transplantation. Transplantation 77(6), 835-838 (2004).
30. Kishi Y, Kami M, Oki Y et al. Donor lymphocyte infusion for treatment of life-threatening respiratory syncytial virus infection following bone marrow transplantation. Bone Marrow Transplant. 26(5), 573-576 (2000).
31. 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 93(10), 3550-3557 (1999).
32. van Dijk AM, Kessler FL, Stadhouders-Keet SA, Verdonck LF, de Gast GC, Otten HG. Selective depletion of major and minor histocompatibility antigen reactive T cells: towards prevention of acute graft-versus-host disease. Br. J. Haematol. 107(1), 169-175 (1999).
33. Andre-Schmutz I, Le DF, Hacein-Bey-Abina S et al. Immune reconstitution without graft-versus-host disease after haemopoietic stem-cell transplantation: A Phase 1/2 study. Lancet 360(9327), 130-137 (2002).
34. Amrolia PJ, Muccioli-Casadei G, Yvon E et al. Selective depletion of donor alloreactive T cells without loss of antiviral or antileukemic responses. Blood 102(6), 2292-2299 (2003).
35. Albon SJ, Mancao C, Gilmour K et al. Optimization of methodology for production of CD25/CD71 allodepleted donor T cells for clinical use. Cytotherapy 15(1), 109-121 (2013).
36. Wehler TC, Nonn M, Brandt B et al. Targeting the activation-induced antigen CD137 can selectively deplete alloreactive T cells from antileukemic and antitumor donor T-cell lines. Blood 109(1), 365-373 (2007).
37. 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 108(6), 1797-1808 (2006).
38. Ge X, Brown J, Sykes M, Boussiotis VA. CD134-allodepletion allows selective elimination of alloreactive human T cells without loss of virus-specific and leukemia-specific effectors. Biol. Blood Marrow Transplant. 14(5), 518-530 (2008).
39. Hartwig UF, Nonn M, Khan S, Meyer RG, Huber C, Herr W. Depletion of alloreactive T cells via CD69: implications on antiviral, antileukemic and immunoregulatory T lymphocytes. Bone Marrow Transplant. 37(3), 297-305 (2006).
40. 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 115(2), 396-407 (2010).
41. Nonn M, Herr W, Khan S et al. Selective depletion of alloreactive T lymphocytes using patient-derived nonhematopoietic stimulator cells in allograft engineering. Transplantation 86(10), 1427-1435 (2008).
42. Solomon SR, Tran T, Carter CS 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 4(5), 395-406 (2002).
43. 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. 15(4), 591-594 (1995).
44. de Vries E, van Tol MJ, van den Bergh RL et al. Reconstitution of lymphocyte subpopulations after paediatric bone marrow transplantation. Bone Marrow Transplant. 25(3), 267-275 (2000).
45. Solomon SR, Mielke S, Savani BN et al. Selective depletion of alloreactive donor lymphocytes: A novel method to reduce the severity of graft-versus-host disease in older patients undergoing matched sibling donor stem cell transplantation. Blood 106(3), 1123-1129 (2005).
46. Mielke S, Nunes R, Rezvani K et al. A clinical-scale selective allodepletion approach for the treatment of HLA-mismatched and matched donor-recipient pairs using expanded T lymphocytes as antigen-presenting cells and a TH9402-based photodepletion technique. Blood 111(8), 4392-4402 (2008).
47. Mielke S, McIver ZA, Shenoy A et al. Selectively T cell-depleted allografts from HLA-matched sibling donors followed by low-dose posttransplantation immunosuppression to improve transplantation outcome in patients with hematologic malignancies. Biol. Blood Marrow Transplant. 17(12), 1855-1861 (2011).
48. McIver ZA, Melenhorst JJ, Grim A et al. Immune reconstitution in recipients of photodepleted HLA-identical sibling donor stem cell transplantations: T cell subset frequencies predict outcome. Biol. Blood Marrow Transplant. 17(12), 1846-1854 (2011).
49. Roy DC, Maertens J, Walker I et al. Selective photodepletion of recipient-alloreactive T-cells enables safe and efficatious haploidentical HSCT: initial results from a Phase 2 trial in patients with AML, ALL and MDS. Blood 124, Abstract 314 (2014).
50. Perruccio K, Topini F, Tosti A et al. Optimizing a photoallodepletion protocol for adoptive immunotherapy after haploidentical SCT. Bone Marrow Transplant. 47(9), 1196-1200 (2012).
51. Davies JK, Gribben JG, Brennan LL, Yuk D, Nadler LM, Guinan EC. Outcome of alloanergized haploidentical bone marrow transplantation after ex vivo costimulatory blockade: results of 2 Phase 1 studies. Blood 112(6), 2232-2241 (2008).
52. Aversa F, Terenzi A, Tabilio A et al. Full haplotype-mismatched hematopoietic stem-cell transplantation: A Phase II study in patients with acute leukemia at high risk of relapse. J. Clin. Oncol. 23(15), 3447-3454 (2005).
53. Davies JK, Barbon CM, Voskertchian AR, Nadler LM, Guinan EC. Induction of alloantigen-specific anergy in human peripheral blood mononuclear cells by alloantigen stimulation with co-stimulatory signal blockade. J. Vis. Exp. 49, pii: 2673 (2011) (Epub ahead of print).
54. Beltinger C, Fulda S, Kammertoens T, Meyer E, Uckert W, Debatin KM. Herpes simplex virus thymidine kinase/ ganciclovir-induced apoptosis involves ligand-independent death receptor aggregation and activation of caspases. Proc. Natl. Acad. Sci. USA 96(15), 8699-8704 (1999).
55. 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. 10(5), 489-500 (2009).
56. Vago L, Oliveira G, Bondanza A et al. T-cell suicide gene therapy prompts thymic renewal in adults after hematopoietic stem cell transplantation. Blood 120(9), 1820-1830 (2012).
57. 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 109(11), 4708-4715 (2007).
58. Tey SK, Dotti G, Rooney CM, Heslop HE, Brenner MK. Inducible caspase 9 suicide gene to improve the safety of allodepleted T cells after haploidentical stem cell transplantation. Biol. Blood Marrow Transplant. 13(8), 913-924 (2007).
59. Di Stasi A, Tey SK, Dotti G et al. Inducible apoptosis as a safety switch for adoptive cell therapy. N. Engl. J. Med. 365(18), 1673-1683 (2011).
60. Zhou X, Di SA, 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 123(25), 3895-3905 (2014).
61. Rezvani K, Mielke S, Ahmadzadeh M et al. 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).
62. 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 117(3), 1061-1070 (2011).
63. Di Ianni M, Falzetti F, Carotti A et al. Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation. Blood 117(14), 3921-3928 (2011).
64. Martelli MF, Di IM, Ruggeri L et al. HLA-haploidentical transplantation with regulatory and conventional T-cell adoptive immunotherapy prevents acute leukemia relapse. Blood 124(4), 638-644 (2014).
65. 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. 202(3), 379-386 (2005).
66. Uhlin M, Gertow J, Uzunel M et al. Rapid salvage treatment with virus-specific T cells for therapy-resistant disease. Clin. Infect. Dis. 55(8), 1064-1073 (2012).
67. Maile R, Wang B, Schooler W, Meyer A, Collins EJ, Frelinger JA. Antigen-specific modulation of an immune response by in vivo administration of soluble MHC class I tetramers. J. Immunol. 167(7), 3708-3714 (2001).
68. O'Herrin SM, Slansky JE, Tang Q et al. Antigen-specific blockade of T cells in vivo using dimeric MHC peptide. J. Immunol. 167(5), 2555-2560 (2001).
69. 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. 8(6), 631-637 (2002).
70. Neudorfer J, Schmidt B, Huster KM et al. Reversible HLA multimers (Streptamers) for the isolation of human cytotoxic T lymphocytes functionally active against tumor-and virus-derived antigens. J. Immunol. Methods 320(1-2), 119-131 (2007).
71. 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 51(3), 591-599 (2011).
72. Buchholz VR, Flossdorf M, Hensel I et al. Disparate individual fates compose robust CD8+ T cell immunity. Science 340(6132), 630-635 (2013).
73. Stemberger C, Graef P, Odendahl M et al. Lowest numbers of primary CD8(+) T cells can reconstitute protective immunity upon adoptive immunotherapy. Blood 124(4), 628-637 (2014).
74. 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. 134(1), 64-76 (2006).
75. 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 116(20), 4360-4367 (2010).
76. Peggs KS, Thomson K, Samuel E et al. Directly selected cytomegalovirus-reactive donor T cells confer rapid and safe systemic reconstitution of virus-specific immunity following stem cell transplantation. Clin. Infect. Dis. 52(1), 49-57 (2011).
77. Moosmann A, Bigalke I, Tischer J et al. Effective and long-term control of EBV PTLD after transfer of peptide-selected T cells. Blood 115(14), 2960-2970 (2010).
78. Icheva V, Kayser S, Wolff D et al. Adoptive transfer of epstein-barr virus (EBV) nuclear antigen 1-specific t cells as treatment for EBV reactivation and lymphoproliferative disorders after allogeneic stem-cell transplantation. J. Clin. Oncol. 31(1), 39-48 (2013).
79. 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. 333(16), 1038-1044 (1995).
80. 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 99(11), 3916-3922 (2002).
81. Peggs KS, Verfuerth S, Pizzey A, Chow SL, Thomson K, Mackinnon S. Cytomegalovirus-specific T cell immunotherapy promotes restoration of durable functional antiviral immunity following allogeneic stem cell transplantation. Clin. Infect. Dis. 49(12), 1851-1860 (2009).
82. Blyth E, Clancy L, Simms R et al. Donor-derived CMV-specific T cells reduce the requirement for CMV-directed pharmacotherapy after allogeneic stem cell transplantation. Blood 121(18), 3745-3758 (2013).
83. Hislop AD, Taylor GS, Sauce D, Rickinson AB. Cellular responses to viral infection in humans: lessons from Epstein-Barr virus. Annu. Rev. Immunol. 25, 587-617 (2007).
84. Rooney CM, Smith CA, Ng CY et al. Use of gene-modified virus-specific T lymphocytes to control Epstein-Barr-virus-related lymphoproliferation. Lancet 345(8941), 9-13 (1995).
85. Rooney CM, Heslop HE, Brenner MK. EBV specific CTL: A model for immune therapy. Vox Sang. 74(Suppl. 2), 497-498 (1998).
86. Heslop H, Rooney C, Brenner M et al. Administration of neomycin resistance gene-marked EBV-specific cytotoxic T-lymphocytes as therapy for patients receiving a bone marrow transplant for relapsed EBV-positive Hodgkin disease. Hum. Gene Ther. 11(10), 1465-1475 (2000).
87. Heslop HE, Slobod KS, Pule MA et al. Long-term outcome of EBV-specific T-cell infusions to prevent or treat EBV-related lymphoproliferative disease in transplant recipients. Blood 115(5), 925-935 (2010).
88. Doubrovina E, Oflaz-Sozmen B, Prockop SE et al. Adoptive immunotherapy with unselected or EBV-specific T cells for biopsy-proven EBV+ lymphomas after allogeneic hematopoietic cell transplantation. Blood 119(11), 2644-2656 (2012).
89. Gustafsson A, Levitsky V, Zou JZ 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 95(3), 807-814 (2000).
90. Comoli P, Basso S, Zecca M et al. Preemptive therapy of EBV-related lymphoproliferative disease after pediatric haploidentical stem cell transplantation. Am. J. Transplant. 7(6), 1648-1655 (2007).
91. Gottschalk S, Ng CY, Perez M et al. An Epstein-Barr virus deletion mutant associated with fatal lymphoproliferative disease unresponsive to therapy with virus-specific CTLs. Blood 97(4), 835-843 (2001).
92. 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. 12(10), 1160-1166 (2006).
93. Leen AM, Christin A, Myers GD et al. Cytotoxic T lymphocyte therapy with donor T cells prevents and treats adenovirus and Epstein-Barr virus infections after haploidentical and matched unrelated stem cell transplantation. Blood 114(19), 4283-4292 (2009).
94. Myers GD, Bollard CM, Wu MF et al. Reconstitution of adenovirus-specific cell-mediated immunity in pediatric patients after hematopoietic stem cell transplantation. Bone Marrow Transplant. 39(11), 677-686 (2007).
95. 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. 17(9), 1616-1625 (2009).
96. 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. 21(11), 2113-2121 (2013).
97. Gerdemann U, Keirnan JM, Katari UL et al. Rapidly generated multivirus-specific cytotoxic T lymphocytes for the prophylaxis and treatment of viral infections. Mol. Ther. 20(8), 1622-1632 (2012).
98. 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. 33(3), 305-315 (2010).
99. 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. 6(242), 242ra83 (2014).
100. Quintarelli C, Dotti G, De AB et al. Cytotoxic T lymphocytes directed to the preferentially expressed antigen of melanoma (PRAME) target chronic myeloid leukemia. Blood 112(5), 1876-1885 (2008).
101. Szabolcs P, Park KD, Reese M, Marti L, Broadwater G, Kurtzberg J. Coexistent naive phenotype and higher cycling rate of cord blood T cells as compared with adult peripheral blood. Exp. Hematol. 31(8), 708-714 (2003).
102. 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 114(9), 1958-1967 (2009).
103. Hanley PJ, Leen AM, Gee A et al. Multivirus-specific-T-cell therapy for patients after stem cell and cord blood hematopoietic stem cell transplantation. Blood 122, Absract 140 (2013).
104. Haque T, Wilkie GM, Jones MM et al. Allogeneic cytotoxic T-cell therapy for EBV-positive posttransplantation lymphoproliferative disease: results of a Phase 2 multicenter clinical trial. Blood 110(4), 1123-1131 (2007).
105. Vickers MA, Wilkie GM, Robinson N et al. Establishment and operation of a Good Manufacturing Practice-compliant allogeneic epstein-barr virus (EBV)-specific cytotoxic cell bank for the treatment of EBV-associated lymphoproliferative disease. Br. J. Haematol. 167(3), 402-410 (2014).
106. 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 121(26), 5113-5123 (2013).
107. Barker JN, Doubrovina E, Sauter C et al. Successful treatment of EBV-associated posttransplantation lymphoma after cord blood transplantation using third-party EBV-specific cytotoxic T lymphocytes. Blood 116(23), 5045-5049 (2010).
108. Cruz CR, Micklethwaite KP, Savoldo B et al. Infusion of donor-derived CD19-redirected virus-specific T cells for B-cell malignancies relapsed after allogeneic stem cell transplant: A Phase 1 study. Blood 122(17), 2965-2973 (2013).
109. Heslop HE, Perez M, Benaim E, Rochester R, Brenner MK, Rooney CM. Transfer of EBV-specific CTL to prevent EBV lymphoma post bone marrow transplant. J. Clin. Apher. 14(3), 154-156 (1999).
110. Rooney CM, Smith CA, Ng CY et al. Use of gene-modified virus-specific T lymphocytes to control Epstein-Barr-virus-related lymphoproliferation. Lancet 345(8941), 9-13 (1995).