Dendritic cell therapy in an allogeneic-hematopoietic cell transplantation setting: An effective strategy toward better disease control?

Frontiers in Immunology

Volumn 5, Issue MAY, 2014, Pages 1-1

  Plantinga, Maud ^a   de Haar, Colin ^a   Nierkens, Stefan ^a   Boelens, Jaap Jan ^a  

^a UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

Author keywords

DC vaccination; Disease control; Hematopoietic cell transplantation; Relapse; T cell responses

Indexed keywords

CD14 ANTIGEN; CD34 ANTIGEN; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; DENDRITIC CELL VACCINE; FAS LIGAND; HLA ANTIGEN; INTERLEUKIN 1BETA; INTERLEUKIN 6; KEYHOLE LIMPET HEMOCYANIN; MUCIN 1; MYELOBLASTIN; PROGRAMMED DEATH 1 RECEPTOR; PROSTAGLANDIN E2; SMALL INTERFERING RNA; THYMOCYTE ANTIBODY; TOLL LIKE RECEPTOR; TUMOR ANTIGEN; TUMOR NECROSIS FACTOR; TUMOR SPECIFIC TRANSPLANTATION ANTIGEN; WT1 PROTEIN;

ACUTE GRANULOCYTIC LEUKEMIA; ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION; ANTIGEN EXPRESSION; ANTIGEN SPECIFICITY; CANCER IMMUNOTHERAPY; CANCER RECURRENCE; CD8+ T LYMPHOCYTE; CELL MATURATION; CELL STIMULATION; CORD BLOOD STEM CELL TRANSPLANTATION; DENDRITIC CELL; DOWN REGULATION; DRUG EFFICACY; DRUG MONITORING; DRUG SAFETY; ENZYME LINKED IMMUNOSORBENT ASSAY; ENZYME LINKED IMMUNOSPOT ASSAY; FLOW CYTOMETRY; GENE TRANSFER; GRAFT VERSUS HOST REACTION; GRAFT VERSUS LEUKEMIA EFFECT; HUMAN; IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME; IMMUNE RESPONSE; IMMUNOREGULATION; NONHUMAN; REVIEW; T LYMPHOCYTE; UPREGULATION; VACCINATION;

EID: 84905397939     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2014.00218     Document Type: Review

References (90)

1. Shaw PJ, Kan F, Woo Ahn K, Spellman SR, Aljurf M, Ayas M, et al. Outcomes of pediatric bone marrow transplantation for leukemia and myelodysplasia using matched sibling, mismatched related, or matched unrelated donors. Blood (2010) 116:4007-15. doi: 10.1182/blood-2010-01-261958
2. Eapen M, Rubinstein P, Zhang M-J, Stevens C, Kurtzberg J, Scaradavou A, et al. Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia: a comparison study. Lancet (2007) 369:1947-54. doi:10.1016/S0140-6736(07)60915-5
3. Leung W, Campana D, Yang J, Pei D, Coustan-Smith E, Gan K, et al. High success rate of hematopoietic cell transplantation regardless of donor source in children with very high-risk leukemia. Blood (2011) 118:223-30. doi:10.1182/blood-2011-01-333070
4. Levenga H, Schaap N, Maas F, Esendam B, Fredrix H, Greupink-Draaisma A, et al. Partial T cell-depleted allogeneic stem cell transplantation following reduced-intensity conditioning creates a platform for immunotherapy with donor lymphocyte infusion and recipient dendritic cell vaccination in multiple myeloma. Biol Blood Marrow Transplant (2010) 16:320-32. doi:10.1016/j.bbmt.2009.10.006
5. Kalos M, June CH. Adoptive T cell transfer for cancer immunotherapy in the era of synthetic biology. Immunity (2013) 39:49-60. doi:10.1016/j.immuni.2013.07.002
6. Ho VT, Vanneman M, Kim H, Sasada T, Kang YJ, Pasek M, et al. Biologic activity of irradiated, autologous, GM-CSF-secreting leukemia cell vaccines early after allogeneic stem cell transplantation. Proc Natl Acad Sci U S A (2009) 106:15825-30. doi:10.1073/pnas.0908358106
7. Rousseau RF. Immunotherapy of high-risk acute leukemia with a recipient (autologous) vaccine expressing transgenic human CD40L and IL-2 after chemotherapy and allogeneic stem cell transplantation. Blood (2006) 107:1332-41. doi:10.1182/blood-2005-03-1259
8. Hsu FJ, Benike C, Fagnoni F, Liles TM, Czerwinski D, Taidi B, et al. Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells. Nat Med (1996) 2:52-8. doi:10.1038/nm0196-52
9. Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med (2010) 363:411-22. doi:10.1056/NEJMoa1001294
10. Laporte JP, Gorin NC, Rubinstein P, Lesage S, Portnoi MF, Barbu V, et al. Cord-blood transplantation from an unrelated donor in an adult with chronic myelogenous leukemia. N Engl J Med (1996) 335:167-70. doi:10.1056/NEJM199607183350304
11. Laughlin MJ, Rizzieri DA, Smith CA, Moore JO, Lilly S, McGaughey D, et al. Hematologic engraftment and reconstitution of immune function post unrelated placental cord blood transplant in an adult with acute lymphocytic leukemia. Leuk Res (1998) 22:215-9. doi:10.1016/S0145-2126(97)00171-9
12. Beelen DW, Ottinger HD, Elmaagacli A, Scheulen B, Basu O, Kremens B, et al. Transplantation of filgrastim-mobilized peripheral blood stem cells from HLA-identical sibling or alternative family donors in patients with hematologic malignancies: a prospective comparison on clinical outcome, immune reconstitution, and hematopoietic chimerism. Blood (1997) 90:4725-35.
13. Brunstein CG, Gutman JA, Weisdorf DJ, Woolfrey AE, DeFor TE, Gooley TA, et al. Allogeneic hematopoietic cell transplantation for hematologic malignancy: relative risks and benefits of double umbilical cord blood. Blood (2010) 116:4693-9. doi:10.1182/blood-2010-05-285304
14. Fricke S, Hilger N, Fricke C, Schönfelder U, Behre G, Ruschpler P, et al. Prevention of graft-versus-host-disease with preserved graft-versus-leukemia-effect by ex vivo and in vivo modulation of CD4(+) T-cells. Cell Mol Life Sci (2013) 71:1-14. doi:10.1007/s00018-013-1476-0
15. Rezvani K, Yong ASM, Savani BN, Mielke S, Keyvanfar K, Gostick E, et al. Graft-versus-leukemia effects associated with detectable Wilms tumor-1-specific T lymphocytes after allogeneic stem-cell transplantation for acute lymphoblastic leukemia. Blood (2007) 110:1924-32. doi:10.1182/blood-2007-03-076844
16. Kapp M, Stevanovic S, Fick K, Tan SM, Loeffler J, Opitz A, et al. CD8+ T-cell responses to tumor-associated antigens correlate with superior relapse-free survival after allo-SCT. Bone Marrow Transplant (2009) 43:399-410. doi:10.1038/bmt.2008.426
17. Weber G, Karbach J, Kuçi S, Kreyenberg H, Willasch A, Koscielniak E, et al. WT1 peptide-specific T cells generated from peripheral blood of healthy donors: possible implications for adoptive immunotherapy after allogeneic stem cell transplantation. Leukemia (2009) 23:1634-42. doi:10.1038/leu.2009.70
18. Rubinstein P, Carrier C, Scaradavou A, Kurtzberg J, Adamson J, Migliaccio AR, et al. Outcomes among 562 recipients of placental-blood transplants from unrelated donors. N Engl J Med (1998) 339:1565-77. doi:10.1056/NEJM199811263392201
19. Rocha V, Wagner JE, Sobocinski KA, Klein JP, Zhang MJ, Horowitz MM, et al. Graft-versus-host disease in children who have received a cord-blood or bone marrow transplant from an HLA-identical sibling. Eurocord and International Bone Marrow Transplant Registry Working Committee on Alternative Donor and Stem Cell Sources. N Engl J Med (2000) 342:1846-54. doi:10.1056/NEJM200006223422501
20. Bracho F, van de Ven C, Areman E, Hughes RM, Davenport V, Bradley MB, et al. A comparison of ex vivo expanded DCs derived from cord blood and mobilized adult peripheral blood plastic-adherent mononuclear cells: decreased alloreactivity of cord blood DCs1. Cytotherapy (2003) 5:349-61. doi:10.1080/14653240310003017
21. Farnault L, Chambost H, Zandotti C, Mallet F, Barlogis V, Galambrun C, et al. Early recovery of immunity after cord-blood transplantation in children: qualitative features and impact of cytomegalovirus infection. Acta Haematol (2012) 128:7-16. doi:10.1159/000337039
22. Clave E, Lisini D, Douay C, Giorgiani G, Busson M, Zecca M, 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. doi:10.3389/fimmu.2013.00054
23. Bartelink IH, Belitser SV, Knibbe CAJ, Danhof M, de Pagter AJ, Egberts TCG, et al. Immune reconstitution kinetics as an early predictor for mortality using various hematopoietic stem cell sources in children. Biol Blood Marrow Transplant (2013) 19:305-13. doi:10.1016/j.bbmt.2012.10.010
24. Lindemans CA, Chiesa R, Amrolia PJ, Rao K, Nikolajeva O, de Wildt A, et al. Impact of thymoglobulin prior to pediatric unrelated umbilical cord blood transplantation on immune reconstitution and clinical outcome. Blood (2014) 123:126-32. doi:10.1182/blood-2013-05-502385
25. Shlomchik WD. Prevention of graft versus host disease by inactivation of host antigen-presenting cells. Science (1999) 285:412-5. doi:10.1126/science.285.5426.412
26. Matte CC, Liu J, Cormier J, Anderson BE, Athanasiadis I, Jain D, et al. Donor APCs are required for maximal GVHD but not for GVL. Nat Med (2004) 10:987-92. doi:10.1038/nm1089
27. Mapara MY. Donor lymphocyte infusions mediate superior graft-versus-leukemia effects in mixed compared to fully allogeneic chimeras: a critical role for host antigen-presenting cells. Blood (2002) 100:1903-9. doi:10.1182/blood-2002-01-0023
28. Toubai T, Sun Y, Luker G, Liu J, Luker KE, Tawara I, et al. Host-derived CD8+ dendritic cells are required for induction of optimal graft-versus-tumor responses after experimental allogeneic bone marrow transplantation. Blood (2013) 121:4231-41. doi:10.1182/blood-2012-05-432872
29. Levenga H, Woestenenk R, Schattenberg AV, Maas F, Jansen JH, Raymakers R, et al. Dynamics in chimerism of T cells and dendritic cells in relapsed CML patients and the influence on the induction of alloreactivity following donor lymphocyte infusion. Bone Marrow Transplant (2007) 40:585-92. doi:10.1038/sj.bmt.1705777
30. Auffermann-Gretzinger S, Lossos IS, Vayntrub TA, Leong W, Grumet FC, Blume KG, et al. Rapid establishment of dendritic cell chimerism in allogeneic hematopoietic cell transplant recipients. Blood (2002) 99:1442-8. doi:10.1182/blood.V99.4.1442
31. Collin MP, Hart DNJ, Jackson GH, Cook G, Cavet J, Mackinnon S, et al. The fate of human Langerhans cells in hematopoietic stem cell transplantation. J Exp Med (2006) 203:27-33. doi:10.1084/jem.20051787
32. Auffermann-Gretzinger S, Eger L, Bornhäuser M, Schäkel K, Oelschlaegel U, Schaich M, et al. Fast appearance of donor dendritic cells in human skin: dynamics of skin and blood dendritic cells after allogeneic hematopoietic cell transplantation. Transplant J (2006) 81:866-73. doi:10.1097/01.tp.0000203318.16224.57
33. Andani R, Robertson I, MacDonald KPA, Durrant S, Hill GR, Khosrotehrani K. Origin of Langerhans cells in normal skin and chronic GVHD after hematopoietic stem-cell transplantation. Exp Dermatol (2013) 23:75-7. doi:10.1111/exd.12301
34. Radford KJ, Tullett KM, Lahoud MH. Science direct dendritic cells and cancer immunotherapy. Curr Opin Immunol (2014) 27:26-32. doi:10.1016/j.coi.2014.01.005
35. Tel J, Aarntzen EHJG, Baba T, Schreibelt G, Schulte BM, Benitez-Ribas D, et al. Natural human plasmacytoid dendritic cells induce antigen-specific T-cell responses in melanoma patients. Cancer Res (2013) 73:1063-75. doi:10.1158/0008-5472.CAN-12-2583
36. Sallusto F, Lanzavecchia A. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha. J Exp Med (1994) 179:1109-18. doi:10.1084/jem.179.4.1109
37. Palucka K, Banchereau J. Cancer immunotherapy via dendritic cells. Nat Rev Cancer (2012) 12:265-77. doi:10.1038/nrc3258
38. Kreutz M, Tacken PJ, Figdor CG. Targeting dendritic cells - why bother? Blood (2013) 121:2836-44. doi:10.1182/blood-2012-09-452078
39. Caux C, Vanbervliet B, Massacrier C, Dezutter-Dambuyant C, de Saint-Vis B, Jacquet C, et al. CD34+ hematopoietic progenitors from human cord blood differentiate along two independent dendritic cell pathways in response to GM-CSF+TNF alpha. J Exp Med (1996) 184:695-706. doi:10.1084/jem.184.2.695
40. Poulin LF, Salio M, Griessinger E, Anjos-Afonso F, Craciun L, Chen JL, et al. Characterization of human DNGR-1+ BDCA3+ leukocytes as putative equivalents of mouse CD8 + dendritic cells. J Exp Med (2010) 207:1261-71. doi:10.1084/jem.20092618
41. Thordardottir S, Hangalapura BN, Hutten T, Cossu M, Spanholtz J, Schaap N, et al. The Aryl hydrocarbon receptor antagonist StemRegenin 1 promotes human plasmacytoid and myeloid dendritic cell development from CD34(+) hematopoietic progenitor cells. Stem Cells Dev (2014) 23(9):955-67. doi:10.1089/scd.2013.0521
42. Troeger A, Meisel R, Moritz T, Dilloo D. Immunotherapy in allogeneic hematopoietic stem cell transplantation - not just a case for effector cells. Bone Marrow Transplant (2005) 35(Suppl 1):S59-64. doi:10.1038/sj.bmt.1704849
43. Banchereau J, Paczesny S, Blanco P, Bennett L, Pascual V, Fay J, et al. Dendritic cells: controllers of the immune system and a new promise for immunotherapy. Ann N Y Acad Sci (2003) 987:180-7. doi:10.1111/j.1749-6632.2003.tb06047.x
44. Nierkens S, Janssen EM. Harnessing dendritic cells for tumor antigen presentation. Cancers (2011) 3:2195-213. doi:10.3390/cancers3022195
45. Kroemer G, Galluzzi L, Kepp O, Zitvogel L. Immunogenic cell death in cancer therapy. Annu Rev Immunol (2013) 31:51-72. doi:10.1146/annurev-immunol-032712-100008
46. Spel L, Boelens JJ, Nierkens S, Boes M. Antitumor immune responses mediated by dendritic cells: how signals derived from dying cancer cells drive antigen cross-presentation. Oncoimmunology (2013) 2:e26403. doi:10.4161/onci.26403
47. Fujii S, Shimizu K, Fujimoto K, Kiyokawa T, Tsukamoto A, Sanada I, et al. Treatment of post-transplanted, relapsed patients with hematological malignancies by infusion of HLA-matched, allogeneic-dendritic cells (DCs) pulsed with irradiated tumor cells and primed T cells. Leuk Lymphoma (2001) 42:357-69. doi:10.3109/10428190109064592
48. Tatsugami K, Eto M, Haarano M, Nagafuji K, Omoto K, Katano M, et al. Dendritic-cell therapy after non-myeloablative stem-cell transplantation for renal-cell carcinoma. Lancet Oncol (2004) 5:750-2. doi:10.1016/S1470-2045(04)01652-3
49. Jonuleit H, Kühn U, Müller G, Steinbrink K, Paragnik L, Schmitt E, et al. Pro-inflammatory cytokines and prostaglandins induce maturation of potent immunostimulatory dendritic cells under fetal calf serum-free conditions. Eur J Immunol (1997) 27:3135-42. doi:10.1002/eji.1830271209
50. Rieser C, Böck G, Klocker H, Bartsch G, Thurnher M. Prostaglandin E2 and tumor necrosis factor alpha cooperate to activate human dendritic cells: synergistic activation of interleukin 12 production. J Exp Med (1997) 186:1603-8.
51. Scandella E, Men Y, Gillessen S, Förster R, Groettrup M. Prostaglandin E2 is a key factor for CCR7 surface expression and migration of monocyte-derived dendritic cells. Blood (2002) 100:1354-61. doi:10.1182/blood-2001-11-0017
52. Braun D, Longman RS, Albert ML. A two-step induction of indoleamine 2,3 dioxygenase (IDO) activity during dendritic-cell maturation. Blood (2005) 106:2375-81. doi:10.1182/blood-2005-03-0979
53. Krause P, Singer E, Darley PI, Klebensberger J, Groettrup M, Legler DF. Prostaglandin E2 is a key factor for monocyte-derived dendritic cell maturation: enhanced T cell stimulatory capacity despite IDO. J Leukoc Biol (2007) 82:1106-14. doi:10.1189/jlb.0905519
54. Vanderlocht J, Van Elssen CHMJ, Senden-Gijsbers BLMG, Meek B, Cloosen S, Libon C, et al. Increased tumor-specific CD8+ T cell induction by dendritic cells matured with a clinical grade TLR-agonist in combination with IFN-gamma. Int J Immunopathol Pharmacol (2010) 23:35-50.
55. Prins RM, Soto H, Konkankit V, Odesa SK, Eskin A, Yong WH, et al. Gene expression profile correlates with T-cell infiltration and relative survival in glioblastoma patients vaccinated with dendritic cell immunotherapy. Clin Cancer Res (2011) 17:1603-15. doi:10.1158/1078-0432.CCR-10-2563
56. Dohnal AM, Witt V, Hügel H, Holter W, Gadner H, Felzmann T. Phase I study of tumor Ag-loaded IL-12 secreting semi-mature DC for the treatment of pediatric cancer. Cytotherapy (2007) 9:755-70. doi:10.1080/14653240701589221
57. Hemont C, Neel A, Heslan M, Braudeau C, Josien R. Human blood mDC subsets exhibit distinct TLR repertoire and responsiveness. J Leukoc Biol (2013) 93:599-609. doi:10.1189/jlb.0912452
58. Wilgenhof S, Van Nuffel AMT, Corthals J, Heirman C, Tuyaerts S, Benteyn D, et al. Therapeutic vaccination with an autologous mRNA electroporated dendritic cell vaccine in patients with advanced melanoma. J Immunother (2011) 34:448-56. doi:10.1097/CJI.0b013e31821dcb31
59. Koski GK, Koldovsky U, Xu S, Mick R, Sharma A, Fitzpatrick E, et al. A novel dendritic cell-based immunization approach for the induction of durable Th1-polarized anti-HER-2/neu responses in women with early breast cancer. J Immunother (2012) 35:54-65. doi:10.1097/CJI.0b013e318235f512
60. Alfaro C, Perez-Gracia JL, Suarez N, Rodriguez J, Fernandez de Sanmamed M, Sangro B, et al. Pilot clinical trial of type 1 dendritic cells loaded with autologous tumor lysates combined with GM-CSF, pegylated IFN, and cyclophosphamide for metastatic cancer patients. J Immunol (2011) 187:6130-42. doi:10.4049/jimmunol.1102209
61. Akiyama Y, Oshita C, Kume A, Iizuka A, Miyata H, Komiyama M, et al. a-type-1 polarized dendritic cell-based vaccination in recurrent high-grade glioma: a phase I clinical trial. BMC Cancer (2012) 12:623. doi:10.1186/1471-2407-12-623
62. Barth RJ, Fisher DA, Wallace PK, Channon JY, Noelle RJ, Gui J, et al. A randomized trial of ex vivo CD40L activation of a dendritic cell vaccine in colorectal cancer patients: tumor-specific immune responses are associated with improved survival. Clin Cancer Res (2010) 16:5548-56. doi:10.1158/1078-0432.CCR-10-2138
63. Hobo W, Novobrantseva TI, Fredrix H, Wong J, Milstein S, Epstein-Barash H, et al. Improving dendritic cell vaccine immunogenicity by silencing PD-1 ligands using siRNA-lipid nanoparticles combined with antigen mRNA electroporation. Cancer Immunol Immunother (2013) 62(2):285-97. doi:10.1007/s00262-012-1334-1
64. Breton G, Yassine-Diab B, Cohn L, Boulassel M-R, Routy J-P, Sékaly R-P, et al. siRNA knockdown of PD-L1 and PD-L2 in monocyte-derived dendritic cells only modestly improves proliferative responses to Gag by CD8(+) T cells from HIV-1-infected individuals. J Clin Immunol (2009) 29:637-45. doi:10.1007/s10875-009-9313-9
65. Chi K-H, Liu S-J, Li C-P, Kuo H-P, Wang Y-S, Chao Y, et al. Combination of conformal radiotherapy and intratumoral injection of adoptive dendritic cell immunotherapy in refractory hepatoma. J Immunother (2005) 28:129-35. doi:10.1097/01.cji.0000154248.74383.5e
66. Bedrosian I, Mick R, Xu S, Nisenbaum H, Faries M, Zhang P, et al. Intranodal administration of peptide-pulsed mature dendritic cell vaccines results in superior CD8+ T-cell function in melanoma patients. J Clin Oncol (2003) 21:3826-35. doi:10.1200/JCO.2003.04.042
67. Kyte JA, Mu L, Aamdal S, Kvalheim G, Dueland S, Hauser M, et al. Phase I/II trial of melanoma therapy with dendritic cells transfected with autologous tumor-mRNA. Cancer Gene Ther (2006) 13:905-18. doi:10.1038/sj.cgt.7700961
68. Ricupito A, Grioni M, Calcinotto A, Hess Michelini R, Longhi R, Mondino A, et al. Booster vaccinations against cancer are critical in prophylactic but detrimental in therapeutic settings. Cancer Res (2013) 73:3545-54. doi:10.1158/0008-5472.CAN-12-2449
69. Banchereau J, Palucka AK, Dhodapkar M, Burkeholder S, Taquet N, Rolland A, et al. Immune and clinical responses in patients with metastatic melanoma to CD34(+) progenitor-derived dendritic cell vaccine. Cancer Res (2001) 61:6451-8.
70. Aarntzen EHJG, Figdor CG, Adema GJ, Punt CJA, Vries IJM. Dendritic cell vaccination and immune monitoring. Cancer Immunol Immunother (2008) 57:1559-68. doi:10.1007/s00262-008-0553-y
71. Toebes M, Coccoris M, Bins A, Rodenko B, Gomez R, Nieuwkoop NJ, et al. Design and use of conditional MHC class I ligands. Nat Med (2006) 12:246-51. doi:10.1038/nm1360
72. Bakker AH, Hoppes R, Linnemann C, Toebes M, Rodenko B, Berkers CR, et al. Conditional MHC class I ligands and peptide exchange technology for the human MHC gene products HLA-A1, -A3, -A11, and -B7. Proc Natl Acad Sci U S A (2008) 105:3825-30. doi:10.1073/pnas.0709717105
73. Voena C, Ladetto M, Astolfi M, Provan D, Gribben JG, Boccadoro M, et al. A novel nested-PCR strategy for the detection of rearranged immunoglobulin heavy-chain genes in B cell tumors. Leukemia (1997) 10:1793-8.
74. van Tendeloo VF, Van de Velde A, Van Driessche A, Cools N, Anguille S, Ladell K, et al. Induction of complete and molecular remissions in acute myeloid leukemia by Wilms' tumor 1 antigen-targeted dendritic cell vaccination. Proc Natl Acad Sci U S A (2010) 107:13824-9. doi:10.1073/pnas.1008051107
75. Schultz RKR, Baker KS, Boelens JJ, Bollard CM, Egeler RM, Cowan M, et al. Challenges and opportunities for international cooperative studies in pediatric hematopoeitic cell transplantation: priorities of the Westhafen Intercontinental Group. Biol Blood Marrow Transplant (2013) 19:1279-87. doi:10.1016/j.bbmt.2013.07.006
76. Grigoleit GU, Kapp M, Hebart H, Fick K, Beck R, Jahn G, et al. Dendritic cell vaccination in allogeneic stem cell recipients: induction of human cytomegalovirus (HCMV)-specific cytotoxic T lymphocyte responses even in patients receiving a transplant from an HCMV-seronegative donor. J Infect Dis (2007) 196:699-704. doi:10.1086/520538
77. Feuchtinger T, Opherk K, Bicanic O, Schumm M, Grigoleit GU, Hamprecht K, et al. Dendritic cell vaccination in an allogeneic stem cell recipient receiving a transplant from a human cytomegalovirus (HCMV)-seronegative donor: induction of a HCMV-specific T helpercell response. Cytotherapy (2010) 12:945-50. doi:10.3109/14653241003587645
78. Kitawaki T, Kadowaki N, Kondo T, Ishikawa T, Ichinohe T, Teramukai S, et al. Potential of dendritic cell immunotherapy for relapse after allogeneic hematopoietic stem cell transplantation, shown by WT1 peptide- and keyhole-limpet-hemocyanin-pulsed, donor-derived dendritic cell vaccine for acute myeloid leukemia. Am J Hematol (2008) 83:315-7. doi:10.1002/ajh.21127
79. Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity (2013) 39:1-10. doi:10.1016/j.immuni.2013.07.012
80. Kolb H-J, Schmid C, Barrett AJ, Schendel DJ. Graft-versus-leukemia reactions in allogeneic chimeras. Blood (2004) 103:767-76. doi:10.1182/blood-2003-02-0342
81. Auletta JJ, Lazarus HM. Immune restoration following hematopoietic stem cell transplantation: an evolving target. Bone Marrow Transplant (2005) 35:835-57. doi:10.1038/sj.bmt.1704966
82. Alyea EP, DeAngelo DJ, Moldrem J, Pagel JM, Przepiorka D, Sadelin M, et al. NCI First International Workshop on The Biology, Prevention and Treatment of Relapse after Allogeneic Hematopoietic Cell Transplantation: report from the committee on prevention of relapse following allogeneic cell transplantation for hematologic malignancies. Biol Blood Marrow Transplant (2010) 16:1037-69. doi:10.1016/j.bbmt.2010.05.005
83. Norde WJ, Hobo W, van der Voort R, Dolstra H. Coinhibitory molecules in hematologic malignancies: targets for therapeutic intervention. Blood (2012) 120:728-36. doi:10.1182/blood-2012-02-412510
84. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer (2012) 12:252-64. doi:10.1038/nrc3239
85. Rosenblatt J, Glotzbecker B, Mills H, Vasir B, Tzachanis D, Levine JD, et al. PD-1 blockade by CT-011, anti-PD-1 antibody, enhances ex vivo T-cell responses to autologous dendritic cell/myeloma fusion vaccine. J Immunother (2011) 34:409-18. doi:10.1097/CJI.0b013e31821ca6ce
86. Bornhäuser M, Thiede C, Platzbecker U, Kiani A, Oelschlaegel U, Babatz J, et al. Prophylactic transfer of BCR-ABL-, PR1-, and WT1-reactive donor T cells after T cell-depleted allogeneic hematopoietic cell transplantation in patients with chronic myeloid leukemia. Blood (2011) 117:7174-84. doi:10.1182/blood-2010-09-308569
87. Krishnadas DK, Stamer MM, Dunham K, Bao L, Lucas KG. Wilms tumor 1-specific cytotoxic T lymphocytes can be expanded from adult donors and cord blood. Leuk Res (2011) 35:1520-6. doi:10.1016/j.leukres.2011.06.037
88. Provasi E, Genovese P, Lombardo A, Magnani Z, Liu P-Q, Reik A, et al. Editing T cell specificity towards leukemia by zinc finger nucleases and lentiviral gene transfer. Nat Med (2012) 18:807-15. doi:10.1038/nm.2700
89. Frumento G, Zheng Y, Aubert G, Raeiszadeh M, Lansdorp PM, Moss P, et al. Cord blood T cells retain early differentiation phenotype suitable for immunotherapy after TCR gene transfer to confer EBV specificity. Am J Transplant (2012) 13:45-55. doi:10.1111/j.1600-6143.2012.04286
90. Krishnadas DK, Shapiro T, Lucas K. Complete remission following decitabine/dendritic cell vaccine for relapsed neuroblastoma. Pediatrics (2013) 131:e336-41. doi:10.1542/peds.2012-0376