title: Selection and expansion of natural killer cells for NK cell-based immunotherapy.
abstract: Natural killer (NK) cells have been used in several clinical trials as adaptive immunotherapy. The low numbers of these cells in peripheral blood mononuclear cells (PBMC) have resulted in various approaches to preferentially expand primary NK cells from PBMC. While some clinical trials have used the addition of interleukin 2 (IL-2) to co-stimulate the expansion of purified NK cells from allogeneic donors, recent studies have shown promising results in achieving in vitro expansion of NK cells to large numbers for adoptive immunotherapy. NK cell expansion requires multiple cell signals for survival, proliferation and activation. Thus, expansion strategies have been focused either to substitute these factors using autologous feeder cells or to use genetically modified allogeneic feeder cells. Recent developments in the clinical use of genetically modified NK cell lines with chimeric antigen receptors, the development of expansion protocols for the clinical use of NK cell from human embryonic stem cells and induced pluripotent stem cells are challenging improvements for NK cell-based immunotherapy. Transfer of several of these protocols to clinical-grade production of NK cells necessitates adaptation of good manufacturing practice conditions, and the development of freezing conditions to establish NK cell stocks will require some effort and, however, should enhance the therapeutic options of NK cells in clinical medicine.
authors.affiliation: Institute for Transfusion Medicine and Immunohematology, German Red Cross Blood Donation Service Baden-Wuerttemberg-Hessen, Sandhofstrasse 1, 60528, Frankfurt am Main, Germany.
authors.forename: Petra S A
authors.initials: PS
authors.lastname: Becker
authors.affiliation: Institute for Transfusion Medicine, German Red Cross Blood Donor Service North-East, Berlin, Germany.
authors.forename: Garnet
authors.initials: G
authors.lastname: Suck
authors.affiliation: Institute for Transfusion Medicine and Immunohematology, German Red Cross Blood Donation Service Baden-Wuerttemberg-Hessen, Sandhofstrasse 1, 60528, Frankfurt am Main, Germany.
authors.forename: Paulina
authors.initials: P
authors.lastname: Nowakowska
authors.affiliation: Division of Pediatric Stem Cell Transplantation, Johann Wolfgang Goethe University Hospital, Frankfurt am Main, Germany.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Ullrich
authors.affiliation: Institute for Transfusion Medicine and Immunohematology, German Red Cross Blood Donation Service Baden-Wuerttemberg-Hessen, Sandhofstrasse 1, 60528, Frankfurt am Main, Germany.
authors.forename: Erhard
authors.initials: E
authors.lastname: Seifried
authors.affiliation: Division of Pediatric Stem Cell Transplantation, Johann Wolfgang Goethe University Hospital, Frankfurt am Main, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bader
authors.affiliation: Center for Regenerative Therapies Dresden, Carl Gustav Carus University of Technology, Dresden, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Tonn
authors.affiliation: Institute for Transfusion Medicine and Immunohematology, German Red Cross Blood Donation Service Baden-Wuerttemberg-Hessen, Sandhofstrasse 1, 60528, Frankfurt am Main, Germany. c.seidl@blutspende.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Seidl
mesh_terms: D018929:Cell Culture Techniques / Q000379:methods*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000637:transplantation*; D018448:Models, Immunological; D054340:Receptors, KIR / Q000276:immunology
chemical_list: D007376:Interleukin-2; D054340:Receptors, KIR
keywords: Hematopoietic stem cell transplantation; Immunotherapy; Killer cell immunoglobulin-like receptor; Natural killer cells
references.citation: Immunity. 1997 Dec;7(6):753-63
references.pmid: 9430221
references.citation: PLoS One. 2011;6(11):e27351
references.pmid: 22096557
references.citation: Blood. 2009 Jun 11;113(24):6094-101
references.pmid: 19365083
references.citation: Cytotherapy. 2015 Mar;17(3):245-9
references.pmid: 25533934
references.citation: J Hematother Stem Cell Res. 2001 Aug;10(4):535-44
references.pmid: 11522236
references.citation: Hum Immunol. 2015 Sep;76(9):636-43
references.pmid: 26407827
references.citation: Cancer Res. 2009 May 1;69(9):4010-7
references.pmid: 19383914
references.citation: Oncoimmunology. 2013 Oct 1;2(10):e26527
references.pmid: 24404423
references.citation: Front Immunol. 2013 Feb 01;4:15
references.pmid: 23378843
references.citation: Biol Blood Marrow Transplant. 2014 Apr;20(4):463-73
references.pmid: 24434782
references.citation: Semin Immunol. 2014 Apr;26(2):161-72
references.pmid: 24618042
references.citation: Ann Surg. 1989 Oct;210(4):474-84; discussion 484-5
references.pmid: 2679456
references.citation: Exp Hematol. 2011 Sep;39(9):904-14
references.pmid: 21703984
references.citation: N Engl J Med. 2012 Aug 30;367(9):805-16
references.pmid: 22931314
references.citation: PLoS One. 2011;6(6):e20740
references.pmid: 21698239
references.citation: PLoS One. 2013;8(1):e53611
references.pmid: 23326467
references.citation: J Exp Med. 2006 Mar 20;203(3):633-45
references.pmid: 16533882
references.citation: PLoS One. 2014;9(1):e87086
references.pmid: 24489840
references.citation: Exp Hematol. 2008 Jan;36(1):61-8
references.pmid: 18155552
references.citation: Cancer Res. 2013 Apr 15;73(8):2598-607
references.pmid: 23580577
references.citation: Expert Rev Clin Immunol. 2014 Feb;10(2):207-17
references.pmid: 24410537
references.citation: Front Immunol. 2014 Mar 17;5:95
references.pmid: 24672522
references.citation: Blood. 2010 Apr 15;115(15):3162-5
references.pmid: 20124216
references.citation: J Immunol. 2005 Oct 15;175(8):5095-103
references.pmid: 16210613
references.citation: Blood. 2013 Aug 15;122(7):1316-24
references.pmid: 23744585
references.citation: Front Immunol. 2014 Feb 26;5:72
references.pmid: 24616720
references.citation: Blood. 2009 Jan 15;113(3):726-32
references.pmid: 18945962
references.citation: Blood. 2011 May 12;117(19):5152-6
references.pmid: 21415265
references.citation: Leukemia. 1994 Apr;8(4):652-8
references.pmid: 8152260
references.citation: Cytotherapy. 2013 Dec;15(12):1563-70
references.pmid: 24094496
references.citation: Hematology Am Soc Hematol Educ Program. 2013;2013:234-46
references.pmid: 24319186
references.citation: Int J Radiat Biol. 2006 May;82(5):355-61
references.pmid: 16782653
references.citation: Eur J Immunol. 1999 Jan;29(1):277-83
references.pmid: 9933109
references.citation: N Engl J Med. 2014 Nov 20;371(21):2042
references.pmid: 25409391
references.citation: PLoS One. 2012;7(1):e30264
references.pmid: 22279576
references.citation: Bone Marrow Transplant. 2003 Jul;32(2):177-86
references.pmid: 12838283
references.citation: J Immunol. 2008 May 1;180(9):6392-401
references.pmid: 18424763
references.citation: Cytotherapy. 2008;10(6):625-32
references.pmid: 18836917
references.citation: J Transl Med. 2015;13:277
references.pmid: 26303618
references.citation: Blood. 2005 Apr 15;105(8):3051-7
references.pmid: 15632206
references.citation: Cytotherapy. 2012 Aug;14(7):851-9
references.pmid: 22799277
references.citation: Curr Opin Immunol. 2005 Apr;17(2):211-7
references.pmid: 15766683
references.citation: Blood. 2010 Oct 7;116(14):2411-9
references.pmid: 20581313
references.citation: Blood. 2014 Feb 13;123(7):967-73
references.pmid: 24363403
references.citation: Front Immunol. 2014 Mar 07;5:87
references.pmid: 24639677
references.citation: Semin Oncol. 2012 Dec;39(6):643-52
references.pmid: 23206841
references.citation: Science. 2002 Mar 15;295(5562):2097-100
references.pmid: 11896281
references.citation: Haematologica. 2015 Feb;100(2):263-8
references.pmid: 25510242
references.citation: Front Immunol. 2013 Dec 30;4:499
references.pmid: 24416035
references.citation: Cancer Immunol Res. 2014 Sep;2(9):878-89
references.pmid: 24958280
references.citation: Haematologica. 2009 Nov;94(11):1590-4
references.pmid: 19608675
references.citation: Blood. 2014 Oct 23;124(17):2744-7
references.pmid: 25115891
references.citation: J Immunother. 2013 Sep;36(7):373-81
references.pmid: 23924789
references.citation: J Immunol. 2013 May 1;190(9):4650-60
references.pmid: 23554313
references.citation: Front Immunol. 2014 Sep 15;5:439
references.pmid: 25309538
references.citation: Clin Exp Immunol. 2013 Apr;172(1):104-12
references.pmid: 23480190
references.citation: Leukemia. 2015 Oct;29(10):2039-49
references.pmid: 25975191
references.citation: Blood. 2005 Jun 15;105(12):4878-84
references.pmid: 15731175
references.citation: Anticancer Res. 2013 May;33(5):2011-9
references.pmid: 23645750
references.citation: Blood. 2012 Mar 15;119(11):2665-74
references.pmid: 22180440
references.citation: N Engl J Med. 1985 Dec 5;313(23):1485-92
references.pmid: 3903508
references.citation: J Biomed Biotechnol. 2011;2011:379123
references.pmid: 21660134
references.citation: Ann Surg. 1988 Aug;208(2):121-35
references.pmid: 3041925
references.citation: Cytotherapy. 2010 Oct;12(6):750-63
references.pmid: 20491532
references.citation: J Clin Oncol. 2013 Oct 20;31(30):3782-90
references.pmid: 24043749
references.citation: Eur Radiol. 2005 Jan;15(1):4-13
references.pmid: 15616814
references.citation: Front Oncol. 2013 May 17;3:118
references.pmid: 23730623
references.citation: PLoS One. 2010;5(2):e9221
references.pmid: 20169160
references.citation: Stem Cells Transl Med. 2013 Apr;2(4):274-83
references.pmid: 23515118
references.citation: Hematol Oncol Stem Cell Ther. 2010;3(3):135-42
references.pmid: 20890071
references.citation: J Immunol. 2005 May 15;174(10):6540-5
references.pmid: 15879158
references.citation: Crit Rev Oncol Hematol. 2015 Aug;95(2):179-90
references.pmid: 25819749
references.citation: Stem Cells Dev. 2013 Jul 1;22(13):1861-9
references.pmid: 23421330
references.citation: Front Immunol. 2015 Apr 28;6:195
references.pmid: 25972867
references.citation: Cell Commun Adhes. 2011 Jun;18(3):45-55
references.pmid: 21906011