Advances in clinical NK cell studies: Donor selection, manufacturing and quality control

OncoImmunology

Volumn 5, Issue 4, 2016, Pages

  Koehl, U ^a   Kalberer, C ^b   Spanholtz, J ^c   Lee, D A ^d   Miller, J S ^e   Cooley, S ^e   Lowdell, M ^f   Uharek, L ^g   Klingemann, H ^h   Curti, A ⁱ   Leung, W ^j   Alici, E ^k,l  

^a HANNOVER MEDICAL SCHOOL   (Germany)

^b UNIVERSITY HOSPITAL BASEL   (Switzerland)

^c Glycostem Therapeutics   (Netherlands)

^d UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^e UNIVERSITY OF MINNESOTA MEDICAL SCHOOL   (United States)

^f ROYAL FREE AND UNIVERSITY COLLEGE MEDICAL SCHOOL   (United Kingdom)

^g CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^h NantKwest Inc   (United States)

ⁱ UNIVERSITY OF BOLOGNA   (Italy)

^j ST JUDE CHILDREN S RESEARCH HOSPITAL   (United States)

^k KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

^l NOVA SOUTHEASTERN UNIVERSITY   (United States)

more..

Author keywords

Clinical NK cell studies; ex vivo expansion; manufacturing of NK cell products; quality control

Indexed keywords

CANCER IMMUNOTHERAPY; CLINICAL TRIAL; DONOR SELECTION; HUMAN; NATURAL KILLER CELL; QUALITY CONTROL;

EID: 84962886163     PISSN: 21624011     EISSN: 2162402X     Source Type: Journal    
DOI: 10.1080/2162402X.2015.1115178     Document Type: Review

References (89)

1. M.Stern, J.R.Passweg, S.Meyer-Monard, R.Esser, T.Tonn, J.Soerensen, M.Paulussen, A.Gratwohl, T.Klingebiel, P.Bader et al. Pre-emptive immunotherapy with purified natural killer cells after haploidentical SCT: a prospective phase II study in two centers. Bone Marrow Transplant 2013; 48:433-8; PMID:22941380; http://dx.doi.org/10.1038/bmt.2012.162
2. J.S.Miller, Y.Soignier, A.Panoskaltsis-Mortari, S.A.McNearney, G.H.Yun, S.K.Fautsch, D.McKenna, C.Le, T.E.Defor, L.J.Burns et al. Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood 2005; 105:3051-7; PMID:15632206; http://dx.doi.org/10.1182/blood-2004-07-2974
3. L.Ruggeri, M.Capanni, E.Urbani, K.Perruccio, W.D.Shlomchik, A.Tosti, S.Posati, D.Rogaia, F.Frassoni, F.Aversa et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science 2002; 295:2097-100; PMID:11896281; http://dx.doi.org/10.1126/science.1068440
4. F.Locatelli, D.Pende, M.C.Mingari, A.Bertaina, M.Falco, A.Moretta, L.Moretta. Cellular and molecular basis of haploidentical hematopoietic stem cell transplantation in the successful treatment of high-risk leukemias: role of alloreactive NK cells. Front Immunol 2013; 4:15; PMID:23378843; http://dx.doi.org/10.3389/fimmu.2013.00015
5. H.Klingemann. Are natural killer cells superior CAR drivers? Oncoimmunology 2014; 3:e28147; PMID:25340009; http://dx.doi.org/10.4161/onci.28147
6. W.Glienke, R.Esser, C.Priesner, J.D.Suerth, A.Schambach, W.S.Wels, M.Grez, S.Kloess, L.Arseniev, U.Koehl. Advantages and applications of CAR-expressing natural killer cells. Front Pharmacol 2015; 6:21; PMID:25729364; http://dx.doi.org/10.3389/fphar.2015.00021
7. S.Huenecke, S.Y.Zimmermann, S.Kloess, R.Esser, A.Brinkmann, L.Tramsen, M.Koenig, S.Erben, C.Seidl, T.Tonn et al. IL-2-driven regulation of NK cell receptors with regard to the distribution of CD16+ and CD16- subpopulations and in vivo influence after haploidentical NK cell infusion. J Immunother 2010; 33:200-10; PMID:20145545; http://dx.doi.org/10.1097/CJI.0b013e3181bb46f7
8. C.Brehm, S.Huenecke, A.Quaiser, R.Esser, M.Bremm, S.Kloess, J.Soerensen, H.Kreyenberg, C.Seidl, P.S.Becker et al. IL-2 stimulated but not unstimulated NK cells induce selective disappearance of peripheral blood cells: concomitant results to a phase I/II study. PloS One 2011; 6:e27351; PMID:22096557; http://dx.doi.org/10.1371/journal.pone.0027351
9. S.Kloess, S.Huenecke, D.Piechulek, R.Esser, J.Koch, C.Brehm, J.Soerensen, T.Gardlowski, A.Brinkmann, P.Bader et al. IL-2-activated haploidentical NK cells restore NKG2D-mediated NK-cell cytotoxicity in neuroblastoma patients by scavenging of plasma MICA. Eur J Immunol 2010; 40:3255-67; PMID:21061445; http://dx.doi.org/10.1002/eji.201040568
10. E.Ullrich, J.Koch, A.Cerwenka, A.Steinle. New prospects on the NKG2D/NKG2DL system for oncology. Oncoimmunology 2013; 2:e26097; PMID:24353908; http://dx.doi.org/10.4161/onci.26097
11. C.Brehm, S.Huenecke, R.Esser, S.Kloess, A.Quaiser, S.Betz, O.Zimmermann, J.Soerensen, J.R.Passweg, T.Klingebiel et al. Interleukin-2-stimulated natural killer cells are less susceptible to mycophenolate mofetil than non-activated NK cells: possible consequences for immunotherapy. Cancer Immunol Immunother 2014; 63:821-33; PMID:24806448; http://dx.doi.org/10.1007/s002-62-014-1556-5
12. R.Esser, T.Muller, D.Stefes, S.Kloess, D.Seidel, S.D.Gillies, C.Aperlo-Iffland, J.S.Huston, C.Uherek, K.Schonfeld et al. NK cells engineered to express a GD2 -specific antigen receptor display built-in ADCC-like activity against tumour cells of neuroectodermal origin. J Cell Mol Med 2012; 16:569-81; PMID:21595822; http://dx.doi.org/10.1111/j.1582-4934.2011.01343.x
13. K.Schonfeld, C.Sahm, C.Zhang, S.Naundorf, C.Brendel, M.Odendahl, P.Nowakowska, H.Bonig, U.Kohl, S.Kloess et al. Selective inhibition of tumor growth by clonal NK cells expressing an ErbB2/HER2-specific chimeric antigen receptor. Mol Ther 2015; 23:330-8; PMID:25373520; http://dx.doi.org/10.1038/mt.2014.219
14. U.Siegler, S.Meyer-Monard, S.Jorger, M.Stern, A.Tichelli, A.Gratwohl, A.Wodnar-Filipowicz, C.P.Kalberer. Good manufacturing practice-compliant cell sorting and large-scale expansion of single KIR-positive alloreactive human natural killer cells for multiple infusions to leukemia patients. Cytotherapy 2010; 12:750-63; PMID:20491532; http://dx.doi.org/10.3109/14653241003786155
15. S.Meyer-Monard, J.Passweg, U.Siegler, C.Kalberer, U.Koehl, A.Rovo, J.Halter, M.Stern, D.Heim, J.R.Alois Gratwohl et al. Clinical-grade purification of natural killer cells in haploidentical hematopoietic stem cell transplantation. Transfusion 2009; 49:362-71; PMID:19389215; http://dx.doi.org/10.1111/j.1537-2995.2008.01969.x
16. E.Alici, T.Sutlu, B.Bjorkstrand, M.Gilljam, B.Stellan, H.Nahi, H.C.Quezada, G.Gahrton, H.G.Ljunggren, M.S.Dilber. Autologous antitumor activity by NK cells expanded from myeloma patients using GMP-compliant components. Blood 2008; 111:3155-62; PMID:18192509; http://dx.doi.org/10.1182/blood-2007-09-110312
17. T.Sutlu, B.Stellan, M.Gilljam, H.C.Quezada, H.Nahi, G.Gahrton, E.Alici. Clinical-grade, large-scale, feeder-free expansion of highly active human natural killer cells for adoptive immunotherapy using an automated bioreactor. Cytotherapy 2010; 12:1044-55; PMID:20795758; http://dx.doi.org/10.3109/14653249.2010.504770
18. J.Cany, H.Dolstra, N.Shah. Umbilical cord blood-derived cellular products for cancer immunotherapy. Cytotherapy. 2015 Jun; 17(6):739-48; http://dx.doi.org/10.1016/j.jcyt.2015.03.005
19. J.Spanholtz, M.Tordoir, D.Eissens, F.Preijers, A.van der Meer, I.Joosten, N.Schaap, T.M.de Witte, H.Dolstra. High log-scale expansion of functional human natural killer cells from umbilical cord blood CD34-positive cells for adoptive cancer immunotherapy. PloS One 2010; 5:e9221; PMID:20169160; http://dx.doi.org/10.1371/journal.pone.0009221
20. J.Cany, A.B.van der Waart, J.Spanholtz, M.Tordoir, J.H.Jansen, R.van der Voort, N.M.Schaap, H.Dolstra. Combined IL-15 and IL-12 drives the generation of CD34-derived natural killer cells with superior maturation and alloreactivity potential following adoptive transfer. Oncoimmunology 2015; 4:e1017701; PMID:26140247; http://dx.doi.org/10.1080/2162402X.2015.1017701
21. J.Spanholtz, F.Preijers, M.Tordoir, C.Trilsbeek, J.Paardekooper, T.de Witte, N.Schaap, H.Dolstra. Clinical-grade generation of active NK cells from cord blood hematopoietic progenitor cells for immunotherapy using a closed-system culture process. PloS One 2011; 6:e20740; PMID:21698239; http://dx.doi.org/10.1371/journal.pone.00-20740
22. S.Chouaib, G.Pittari, A.Nanbakhsh, H.El Ayoubi, S.Amsellem, J.H.Bourhis, J.Spanholtz. Improving the outcome of leukemia by natural killer cell-based immunotherapeutic strategies. Front Immunol 2014; 5:95; PMID:24672522; http://dx.doi.org/10.3389/fimmu.2014.00095
23. D.A.Lee, M.R.Verneris, D.Campana. Acquisition, preparation, and functional assessment of human NK cells for adoptive immunotherapy. Methods Mol Biol 2010; 651:61-77; PMID:20686960; http://dx.doi.org/10.1007/978-1-60761-786-0_4
24. N.Shah, B.Martin-Antonio, H.Yang, S.Ku, D.A.Lee, L.J.Cooper, W.K.Decker, S.Li, S.N.Robinson, T.Sekine et al. Antigen presenting cell-mediated expansion of human umbilical cord blood yields log-scale expansion of natural killer cells with anti-myeloma activity. PloS One 2013; 8:e76781; PMID:24204673; http://dx.doi.org/10.1371/journal.pone.0076781
25. S.Zhu, P.V.Phatarpekar, C.J.Denman, V.V.Senyukov, S.S.Somanchi, H.T.Nguyen-Jackson, E.M.Mace, A.F.Freeman, S.S.Watowich, J.S.Orange et al. Transcription of the activating receptor NKG2D in natural killer cells is regulated by STAT3 tyrosine phosphorylation. Blood 2014; 124:403-11; PMID:24891320; http://dx.doi.org/10.1182/blood-2013-05-499707
26. N.Tarek, D.A.Lee. Natural killer cells for osteosarcoma. Adv Exp Med Biol 2014; 804:341-53; PMID:24924184; http://dx.doi.org/10.1007/978-3-319-04843-7_19
27. M.A.Geller, S.Cooley, P.L.Judson, R.Ghebre, L.F.Carson, P.A.Argenta, A.L.Jonson, A.Panoskaltsis-Mortari, J.Curtsinger, D.McKenna et al. A phase II study of allogeneic natural killer cell therapy to treat patients with recurrent ovarian and breast cancer. Cytotherapy 2011; 13:98-107; PMID:20849361; http://dx.doi.org/10.3109/14653249.2010.515582
28. V.Bachanova, L.J.Burns, D.H.McKenna, J.Curtsinger, A.Panoskaltsis-Mortari, B.R.Lindgren, S.Cooley, D.Weisdorf, J.S.Miller. Allogeneic natural killer cells for refractory lymphoma. Cancer Immunol Immunother 2010; 59:1739-44; PMID:20680271; http://dx.doi.org/10.1007/s00262-010-0896-z
29. A.Wiernik, B.Foley, B.Zhang, M.R.Verneris, E.Warlick, M.K.Gleason, J.A.Ross, X.Luo, D.J.Weisdorf, B.Walcheck et al. Targeting Natural Killer Cells to Acute Myeloid Leukemia In Vitro with a CD16´33 Bispecific Killer Cell Engager and ADAM17 Inhibition. Clin Cancer Res 2013; Jul 15; 19(14):3844-55; PMID:23690482; http://dx.doi.org/10.1158/1078-0432.CCR-13-0505
30. J.S.Miller. Therapeutic applications: natural killer cells in the clinic. Hematology Am Soc Hematol Educ Program 2013; 2013:247-53; PMID:24319187; http://dx.doi.org/10.1182/asheducation-2013.1.247
31. P.D.Kottaridis, J.North, M.Tsirogianni, C.Marden, E.R.Samuel, S.Jide-Banwo, S.Grace, M.W.Lowdell. Two-Stage Priming of Allogeneic Natural Killer Cells for the Treatment of Patients with Acute Myeloid Leukemia: A Phase I Trial. PloS One 2015; 10:e0123416; PMID:26062124; http://dx.doi.org/10.1371/journal.pone.0123416
32. E.Katodritou, E.Terpos, J.North, P.Kottaridis, E.Verrou, V.Gastari, C.Chadjiaggelidou, S.Sivakumaran, S.Jide-Banwo, M.Tsirogianni et al. Tumor-primed natural killer cells from patients with multiple myeloma lyse autologous, NK-resistant, bone marrow-derived malignant plasma cells. Am J Hematol 2011; 86:967-73; PMID:21919039; http://dx.doi.org/10.1002/ajh.22163
33. M.Sabry, M.Tsirogianni, I.A.Bakhsh, J.North, J.Sivakumaran, K.Giannopoulos, R.Anderson, S.Mackinnon, M.W.Lowdell. Leukemic priming of resting NK cells is killer Ig-like receptor independent but requires CD15-mediated CD2 ligation and natural cytotoxicity receptors. J Immunol 2011; 187:6227-34; PMID:22084431; http://dx.doi.org/10.4049/jimmunol.1101640
34. M.Sabry, M.W.Lowdell. Tumor-Primed NK Cells: Waiting for the Green Light. Front Immunol 2013; 4:408; PMID:24324471; http://dx.doi.org/10.3389/fimmu.2013.00408
35. L.Fischer, O.Penack, C.Gentilini, A.Nogai, A.Muessig, E.Thiel, L.Uharek. The anti-lymphoma effect of antibody-mediated immunotherapy is based on an increased degranulation of peripheral blood natural killer (NK) cells. Exp Hematol 2006; 34:753-9; PMID:16728280; http://dx.doi.org/10.1016/j.exphem.2006.02.015
36. O.Penack, C.Gentilini, L.Fischer, A.M.Asemissen, C.Scheibenbogen, E.Thiel, L.Uharek. CD56dimCD16neg cells are responsible for natural cytotoxicity against tumor targets. Leukemia 2005; 19:835-40; PMID:15744340; http://dx.doi.org/10.1038/sj.leu.2403704
37. T.Tonn, D.Schwabe, H.G.Klingemann, S.Becker, R.Esser, U.Koehl, M.Suttorp, E.Seifried, O.G.Ottmann, G.Bug. Treatment of patients with advanced cancer with the natural killer cell line NK-92. Cytotherapy 2013; 15:1563-70; PMID:24094496; http://dx.doi.org/10.1016/j.jcyt.2013.06.017
38. H.Klingemann. Challenges of cancer therapy with natural killer cells. Cytotherapy 2015; 17:245-9; PMID:25533934; http://dx.doi.org/10.1016/j.jcyt.2014.09.007
39. Y.K.Tam, J.A.Martinson, K.Doligosa, H.G.Klingemann. Ex vivo expansion of the highly cytotoxic human natural killer-92 cell-line under current good manufacturing practice conditions for clinical adoptive cellular immunotherapy. Cytotherapy 2003; 5:259-72; PMID:12850795; http://dx.doi.org/10.1080/14653240310001523
40. H.G.Klingemann. Cellular therapy of cancer with natural killer cells-where do we stand? Cytotherapy 2013; 15:1185-94; PMID:23768925; http://dx.doi.org/10.1016/j.jcyt.2013.03.011
41. S.A.Koepsell, D.M.Kadidlo, S.Fautsch, J.McCullough, H.Klingemann, J.E.Wagner, J.S.Miller, D.H.McKenna, Jr. Successful “in-flight” activation of natural killer cells during long-distance shipping. Transfusion 2013; 53:398-403; PMID:22574659; http://dx.doi.org/10.1111/j.1537-2995.2012.03695.x
42. H.Klingemann, C.Grodman, E.Cutler, M.Duque, D.Kadidlo, A.K.Klein, K.A.Sprague, K.B.Miller, R.L.Comenzo, T.Kewalramani et al. Autologous stem cell transplant recipients tolerate haploidentical related-donor natural killer cell-enriched infusions. Transfusion 2013; 53:412-8; quiz 1; PMID:22738379; http://dx.doi.org/10.1111/j.1537-2995.2012.03764.x
43. L.Zitvogel, G.Kroemer. Targeting PD-1/PD-L1 interactions for cancer immunotherapy. Oncoimmunology 2012; 1:1223-5; PMID:23243584; http://dx.doi.org/10.4161/onci.21335
44. M.Arpinati, A.Curti. Immunotherapy in acute myeloid leukemia. Immunotherapy 2014; 6:95-106; PMID:24341888; http://dx.doi.org/10.2217/imt.13.152
45. A.Curti, L.Ruggeri, A.D'Addio, A.Bontadini, E.Dan, M.R.Motta, S.Trabanelli, V.Giudice, E.Urbani, G.Martinelli et al. Successful transfer of alloreactive haploidentical KIR ligand-mismatched natural killer cells after infusion in elderly high risk acute myeloid leukemia patients. Blood 2011; 118:3273-9; PMID:21791425; http://dx.doi.org/10.1182/blood-2011-01-329508
46. W.Leung. Infusions of allogeneic natural killer cells as cancer therapy. Clin Cancer Res 2014; 20:3390-400; PMID:24987108; http://dx.doi.org/10.1158/1078-0432.CCR-13-1766
47. W.Leung. Use of NK cell activity in cure by transplant. Br J Haematol 2011; 155:14-29; PMID:21812770; http://dx.doi.org/10.1111/j.1365-2141.2011.08823.x
48. W.Leung, R.Iyengar, V.Turner, P.Lang, P.Bader, P.Conn, D.Niethammer, R.Handgretinger. Determinants of antileukemia effects of allogeneic NK cells. J Immunol 2004; 172:644-50; PMID:14688377; http://dx.doi.org/10.4049/jimmunol.172.1.644
49. V.Beziat, J.Traherne, J.A.Malmberg, M.A.Ivarsson, N.K.Bjorkstrom, C.Retiere, H.G.Ljunggren, J.Michaelsson, J.Trowsdale, K.J.Malmberg. Tracing dynamic expansion of human NK-cell subsets by high-resolution analysis of KIR repertoires and cellular differentiation. Eur J Immunol 2014; 44:2192-6; PMID:24723455; http://dx.doi.org/10.1002/eji.201444464
50. S.Cooley, D.J.Weisdorf, L.A.Guethlein, J.P.Klein, T.Wang, C.T.Le, S.G.Marsh, D.Geraghty, S.Spellman, M.D.Haagenson et al. Donor selection for natural killer cell receptor genes leads to superior survival after unrelated transplantation for acute myelogenous leukemia. Blood 2010; 116:2411-9; PMID:20581313; http://dx.doi.org/10.1182/blood-2010-05-283051
51. R.Bari, P.Rujkijyanont, E.Sullivan, G.Kang, V.Turner, K.Gan, W.Leung. Effect of donor KIR2DL1 allelic polymorphism on the outcome of pediatric allogeneic hematopoietic stem-cell transplantation. J Clin Oncol 2013; 31:3782-90; PMID:24043749; http://dx.doi.org/10.1200/JCO.2012.47.4007
52. E.M.Sullivan, S.Jeha, G.Kang, C.Cheng, B.Rooney, M.Holladay, R.Bari, S.Schell, M.Tuggle, C.H.Pui et al. NK cell genotype and phenotype at diagnosis of acute lymphoblastic leukemia correlate with postinduction residual disease. Clin Cancer Res 2014; 20:5986-94; PMID:25281696; http://dx.doi.org/10.1158/1078-0432.CCR-14-0479
53. S.Cooley, D.J.Weisdorf, L.A.Guethlein, J.P.Klein, T.Wang, S.G.Marsh, S.Spellman, M.D.Haagenson, K.Saeturn, M.Ladner et al. Donor killer cell Ig-like receptor B haplotypes, recipient HLA-C1, and HLA-C mismatch enhance the clinical benefit of unrelated transplantation for acute myelogenous leukemia. J Immunol 2014; 192:4592-600; PMID:24748496; http://dx.doi.org/10.4049/jimmunol.1302517
54. B.Foley, M.Felices, F.Cichocki, S.Cooley, M.R.Verneris, J.S.Miller. The biology of NK cells and their receptors affects clinical outcomes after hematopoietic cell transplantation (HCT). Immunol Rev 2014; 258:45-63; PMID:24517425; http://dx.doi.org/10.1111/imr.12157
55. W.Leung, R.Iyengar, B.Triplett, V.Turner, F.G.Behm, M.S.Holladay, J.Houston, R.Handgretinger. Comparison of killer Ig-like receptor genotyping and phenotyping for selection of allogeneic blood stem cell donors. J Immunol 2005; 174:6540-5; PMID:15879158; http://dx.doi.org/10.4049/jimmunol.174.10.6540
56. R.Bari, T.Bell, W.H.Leung, Q.P.Vong, W.K.Chan, N.Das Gupta, M.Holladay, B.Rooney, W.Leung. Significant functional heterogeneity among KIR2DL1 alleles and a pivotal role of arginine 245. Blood 2009; 114:5182-90; PMID:19828694; http://dx.doi.org/10.1182/blood-2009-07-231977
57. G.Cartron, L.Dacheux, G.Salles, P.Solal-Celigny, P.Bardos, P.Colombat, H.Watier. Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcgammaRIIIa gene. Blood 2002; 99:754-8; PMID:11806974; http://dx.doi.org/10.1182/blood.V99.3.754
58. M.R.Parkhurst, J.P.Riley, M.E.Dudley, S.A.Rosenberg. Adoptive transfer of autologous natural killer cells leads to high levels of circulating natural killer cells but does not mediate tumor regression. Clin Cancer Res 2011; 17:6287-97; PMID:21844012; http://dx.doi.org/10.1158/1078-0432.CCR-11-1347
59. H.Fujisaki, H.Kakuda, N.Shimasaki, C.Imai, J.Ma, T.Lockey, P.Eldridge, W.H.Leung, D.Campana. Expansion of highly cytotoxic human natural killer cells for cancer cell therapy. Cancer Res 2009; 69:4010-7; PMID:19383914; http://dx.doi.org/10.1158/0008-5472.CAN-08-3712
60. M.Berg, A.Lundqvist, P.McCoy, Jr., L.Samsel, Y.Fan, A.Tawab, R.Childs. Clinical-grade ex vivo-expanded human natural killer cells up-regulate activating receptors and death receptor ligands and have enhanced cytolytic activity against tumor cells. Cytotherapy 2009; 11:341-55; PMID:19308771; http://dx.doi.org/10.1080/14653240902807034
61. A.Lundqvist, M.Berg, A.Smith, R.W.Childs. Bortezomib treatment to potentiate the anti-tumor immunity of ex-vivo expanded adoptively infused autologous natural killer cells. J Cancer 2011; 2:383-5; PMID:21750690; http://dx.doi.org/10.7150/jca.2.383
62. J.Luhm, J.M.Brand, P.Koritke, M.Hoppner, H.Kirchner, C.Frohn. Large-scale generation of natural killer lymphocytes for clinical application. J Hematother Stem Cell Res 2002; 11:651-7; PMID:12201953; http://dx.doi.org/10.1089/15258160260194794
63. S.Arai, R.Meagher, M.Swearingen, H.Myint, E.Rich, J.Martinson, H.Klingemann. Infusion of the allogeneic cell line NK-92 in patients with advanced renal cell cancer or melanoma: a phase I trial. Cytotherapy 2008; 10:625-32; PMID:18836917; http://dx.doi.org/10.1080/14653240802301872
64. H.G.Klingemann, J.Martinson. Ex vivo expansion of natural killer cells for clinical applications. Cytotherapy 2004; 6:15-22; PMID:14985163; http://dx.doi.org/10.1080/14653240310004548
65. R.Iyengar, R.Handgretinger, A.Babarin-Dorner, T.Leimig, M.Otto, T.L.Geiger, M.S.Holladay, J.Houston, W.Leung. Purification of human natural killer cells using a clinical-scale immunomagnetic method. Cytotherapy 2003; 5:479-84; PMID:14660043; http://dx.doi.org/10.1080/14653240310003558
66. O.Lim, Y.Lee, H.Chung, J.H.Her, S.M.Kang, M.Y.Jung, B.Min, H.Shin, T.M.Kim, D.S.Heo et al. GMP-compliant, large-scale expanded allogeneic natural killer cells have potent cytolytic activity against cancer cells in vitro and in vivo. PloS One 2013; 8:e53611; PMID:23326467; http://dx.doi.org/10.1371/journal.pone.0053611
67. U.Koehl, C.Brehm, S.Huenecke, S.Y.Zimmermann, S.Kloess, M.Bremm, E.Ullrich, J.Soerensen, A.Quaiser, S.Erben et al. Clinical grade purification and expansion of NK cell products for an optimized manufacturing protocol. Front Oncol 2013; 3:118; PMID:23730623; http://dx.doi.org/10.3389/fonc.2013.00118
68. N.Lapteva, A.G.Durett, J.Sun, L.A.Rollins, L.L.Huye, J.Fang, V.Dandekar, Z.Mei, K.Jackson, J.Vera et al. Large-scale ex vivo expansion and characterization of natural killer cells for clinical applications. Cytotherapy 2012; 14:1131-43; PMID:22900959; http://dx.doi.org/10.3109/14653249.2012.700767
69. J.Tanaka, J.Sugita, S.Shiratori, A.Shigematu, S.Asanuma, K.Fujimoto, M.Nishio, T.Kondo, M.Imamura. Expansion of NK cells from cord blood with antileukemic activity using GMP-compliant substances without feeder cells. Leukemia 2012; 26:1149-52; PMID:22143670; http://dx.doi.org/10.1038/leu.2011.345
70. M.Granzin, S.Soltenborn, S.Muller, J.Kollet, M.Berg, A.Cerwenka, R.W.Childs, V.Huppert. Fully automated expansion and activation of clinical-grade natural killer cells for adoptive immunotherapy. Cytotherapy 2015; 17:621-32; PMID:25881519; http://dx.doi.org/10.1016/j.jcyt.2015.03.611
71. J.R.Passweg, A.Tichelli, S.Meyer-Monard, D.Heim, M.Stern, T.Kuhne, G.Favre, A.Gratwohl. Purified donor NK-lymphocyte infusion to consolidate engraftment after haploidentical stem cell transplantation. Leukemia 2004; 18:1835-8; PMID:15457184; http://dx.doi.org/10.1038/sj.leu.2403524
72. J.E.Rubnitz, H.Inaba, R.C.Ribeiro, S.Pounds, B.Rooney, T.Bell, C.H.Pui, W.Leung. NKAML: a pilot study to determine the safety and feasibility of haploidentical natural killer cell transplantation in childhood acute myeloid leukemia. J Clin Oncol 2010; 28:955-9; PMID:20085940; http://dx.doi.org/10.1200/JCO.2009.24.4590
73. S.Motohashi, A.Ishikawa, E.Ishikawa, M.Otsuji, T.Iizasa, H.Hanaoka, N.Shimizu, S.Horiguchi, Y.Okamoto, S.Fujii et al. A phase I study of in vitro expanded natural killer T cells in patients with advanced and recurrent non-small cell lung cancer. Clin Cancer Res 2006; 12:6079-86; PMID:17028247; http://dx.doi.org/10.1158/1078-0432.CCR-06-0114
74. S.W.Krause, R.Gastpar, R.Andreesen, C.Gross, H.Ullrich, G.Thonigs, K.Pfister, G.Multhoff. Treatment of colon and lung cancer patients with ex vivo heat shock protein 70-peptide-activated, autologous natural killer cells: a clinical phase i trial. Clin Cancer Res 2004; 10:3699-707; PMID:15173076; http://dx.doi.org/10.1158/1078-0432.CCR-03-0683
75. S.R.Yoon, Y.S.Lee, S.H.Yang, K.H.Ahn, J.H.Lee, D.Y.Kim, Y.A.Kang, M.Jeon, M.Seol, S.G.Ryu et al. Generation of donor natural killer cells from CD34(+) progenitor cells and subsequent infusion after HLA-mismatched allogeneic hematopoietic cell transplantation: a feasibility study. Bone Marrow Transplant 2010; 45:1038-46; PMID:19881555; http://dx.doi.org/10.1038/bmt.2009.304
76. L.Barkholt, E.Alici, R.Conrad, T.Sutlu, M.Gilljam, B.Stellan, B.Christensson, H.Guven, N.K.Bjorkstrom, G.Soderdahl et al. Safety analysis of ex vivo-expanded NK and NK-like T cells administered to cancer patients: a phase I clinical study. Immunotherapy 2009; 1:753-64; PMID:20636021; http://dx.doi.org/10.2217/imt.09.47
77. U.Koehl, J.Sorensen, R.Esser, S.Zimmermann, H.P.Gruttner, T.Tonn, C.Seidl, E.Seifried, T.Klingebiel, D.Schwabe. IL-2 activated NK cell immunotherapy of three children after haploidentical stem cell transplantation. Blood Cells Mol Dis 2004; 33:261-6; PMID:15528141; http://dx.doi.org/10.1016/j.bcmd.2004.08.013
78. S.Szmania, N.Lapteva, T.Garg, A.Greenway, J.Lingo, B.Nair, K.Stone, E.Woods, J.Khan, J.Stivers et al. Ex vivo-expanded natural killer cells demonstrate robust proliferation in vivo in high-risk relapsed multiple myeloma patients. J Immunother 2015; 38:24-36; PMID:25415285; http://dx.doi.org/10.1097/CJI.0000000000000059
79. E.G.Iliopoulou, P.Kountourakis, M.V.Karamouzis, D.Doufexis, A.Ardavanis, C.N.Baxevanis, G.Rigatos, M.Papamichail, S.A.Perez. A phase I trial of adoptive transfer of allogeneic natural killer cells in patients with advanced non-small cell lung cancer. Cancer Immunol Immunother 2010; 59:1781-9; PMID:20703455; http://dx.doi.org/10.1007/s00262-010-0904-3
80. N.N.Shah, K.Baird, C.P.Delbrook, T.A.Fleisher, M.E.Kohler, S.Rampertaap, K.Lemberg, C.K.Hurley, D.E.Kleiner, M.S.Merchant et al. Acute GVHD in patients receiving IL-15/4-1BBL activated NK cells following T-cell-depleted stem cell transplantation. Blood 2015; 125:784-92; PMID:25452614; http://dx.doi.org/10.1182/blood-2014-07-592881
81. D.A.Lee. The off-target effects of nonspecific NK cells. Blood 2015; 125:744-5; PMID:25634612; http://dx.doi.org/10.1182/blood-2014-12-616359
82. T.Sutlu, E.Alici. Ex vivo expansion of natural killer cells: a question of function. Cytotherapy 2011; 13(6):767-8; PMID:21375422; http://dx.doi.org/10.3109/14653249.2011.563295.
83. J.S.Miller, S.Oelkers, C.Verfaillie, P.McGlave. Role of monocytes in the expansion of human activated natural killer cells. Blood 1992; 80:2221-9; PMID:1421393
84. M.A.Cooper, J.M.Elliott, P.A.Keyel, L.Yang, J.A.Carrero, W.M.Yokoyama. Cytokine-induced memory-like natural killer cells. Proc Natl Acad Sci U S A 2009; 106:1915-9; PMID:19181844; http://dx.doi.org/10.1073/pnas.0813192106
85. J.Ni, M.Miller, A.Stojanovic, N.Garbi, A.Cerwenka. Sustained effector function of IL-12/15/18-preactivated NK cells against established tumors. J Exp Med 2012; 209:2351-65; http://dx.doi.org/10.1084/jem.20120944
86. M.Keeney, I.Chin-Yee, K.Weir, J.Popma, R.Nayar, D.R.Sutherland. Single platform flow cytometric absolute CD34+ cell counts based on the ISHAGE guidelines. International Society of Hematotherapy and Graft Engineering. Cytometry 1998; 34:61-70; PMID:9579602; http://dx.doi.org/10.1002/(SICI)1097-0320(19980415)34:2%3c61::AID-CYTO1%3e3.0.CO;2-F
87. U.Sack, D.Barnett, G.Y.Demirel, C.Fossat, S.Fricke, N.Kafassi, T.Nebe, K.Psarra, J.Steinmann, C.Lambert. Accreditation of flow cytometry in Europe. Cytometry B Clin Cytom 2013; 84:135-42; PMID:23554222; http://dx.doi.org/10.1002/cyto.b.21079
88. S.Y.Zimmermann, R.Esser, E.Rohrbach, T.Klingebiel, U.Koehl. A novel four-colour flow cytometric assay to determine natural killer cell or T-cell-mediated cellular cytotoxicity against leukaemic cells in peripheral or bone marrow specimens containing greater than 20% of normal cells. J Immunol Methods 2005; 296:63-76; PMID:15680151; http://dx.doi.org/10.1016/j.jim.2004.10.014
89. S.Kloss, K.Bochennek, S.Huenecke, S.Y.Zimmermann, S.Kuci, T.Muller, W.S.Wels, T.Klingebiel, R.Esser, U.Koehl. A novel five-colour flow cytometric assay to determine NK cell cytotoxicity against neuroblastoma and other adherent tumour cells. J Immunol Methods 2007; 325:140-7; PMID:17663991; http://dx.doi.org/10.1016/j.jim.2007.06.013