title: Pluripotent stem cell-derived natural killer cells for cancer therapy.
abstract: Human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) provide an accessible, genetically tractable, and homogenous starting cell population to efficiently study human blood cell development. These cell populations provide platforms to develop new cell-based therapies to treat both malignant and nonmalignant hematological diseases. Our group previously demonstrated the ability of hESC-derived hematopoietic precursors to produce functional natural killer (NK) cells as well as an explanation of the underlying mechanism responsible for the inefficient development of T and B cells from hESCs. hESCs and iPSCs, which can be engineered reliably in vitro, provide an important new model system to study human lymphocyte development and produce enhanced cell-based therapies with the potential to serve as a "universal" source of antitumor lymphocytes. This review will focus on the application of hESC-derived NK cells with currently used and novel therapeutics for clinical trials, barriers to translation, and future applications through genetic engineering approaches.
authors.affiliation: Department of Medicine and Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Knorr
authors.forename: Dan S
authors.initials: DS
authors.lastname: Kaufman
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002292:Carcinoma, Renal Cell / Q000601:surgery; D002454:Cell Differentiation; D002986:Clinical Trials as Topic; D019337:Hematologic Neoplasms / Q000601:surgery*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D007680:Kidney Neoplasms / Q000601:surgery; D007694:Killer Cells, Natural / Q000637:transplantation*; D008214:Lymphocytes / Q000166:cytology / Q000502:physiology; D008545:Melanoma / Q000601:surgery; D051379:Mice; D023421:Models, Animal; D009369:Neoplasms / Q000601:surgery*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000637:transplantation*; D013119:Spinal Cord Injuries / Q000601:surgery; D033581:Stem Cell Transplantation / Q000379:methods*; D013601:T-Lymphocytes / Q000276:immunology
references.citation: Nature. 2009 Jul 2;460(7251):53-9
references.pmid: 19483674
references.citation: Hum Gene Ther. 2009 Nov;20(11):1229-39
references.pmid: 19702437
references.citation: Cell. 2007 Nov 30;131(5):861-72
references.pmid: 18035408
references.citation: Stem Cells. 2010 Jan;28(1):64-74
references.pmid: 19904830
references.citation: Cell. 2008 Sep 5;134(5):877-86
references.pmid: 18691744
references.citation: Clin Cancer Res. 2006 Oct 15;12(20 Pt 1):6106-15
references.pmid: 17062687
references.citation: Ann Surg. 1989 Oct;210(4):474-84; discussion 484-5
references.pmid: 2679456
references.citation: Stem Cells. 2007 Sep;25(9):2206-14
references.pmid: 17556598
references.citation: Blood. 2010 Apr 1;115(13):2592-600
references.pmid: 20110425
references.citation: Immunol Rev. 2006 Dec;214:143-54
references.pmid: 17100882
references.citation: N Engl J Med. 1988 Dec 22;319(25):1676-80
references.pmid: 3264384
references.citation: Nat Immunol. 2008 Jun;9(6):575-80
references.pmid: 18490903
references.citation: Cell Stem Cell. 2010 May 7;6(5):407-11
references.pmid: 20452313
references.citation: J Neurosci. 2005 May 11;25(19):4694-705
references.pmid: 15888645
references.citation: Blood. 2005 Mar 15;105(6):2594-600
references.pmid: 15536148
references.citation: Nature. 2008 Jan 10;451(7175):141-6
references.pmid: 18157115
references.citation: Nat Rev Cancer. 2003 Sep;3(9):666-75
references.pmid: 12951585
references.citation: Science. 1998 Nov 6;282(5391):1145-7
references.pmid: 9804556
references.citation: Proc Natl Acad Sci U S A. 2006 Aug 1;103(31):11742-7
references.pmid: 16844782
references.citation: Proc Natl Acad Sci U S A. 2008 Oct 21;105(42):16254-9
references.pmid: 18838682
references.citation: Blood. 2003 Aug 1;102(3):814-9
references.pmid: 12689936
references.citation: Science. 2009 May 8;324(5928):797-801
references.pmid: 19325077
references.citation: Semin Hematol. 1999 Oct;36(4 Suppl 7):95-103
references.pmid: 10595758
references.citation: Blood. 2009 Jun 11;113(24):6094-101
references.pmid: 19365083
references.citation: J Immunol. 1992 Sep 15;149(6):1876-80
references.pmid: 1387664
references.citation: Nature. 2007 Jul 19;448(7151):318-24
references.pmid: 17554336
references.citation: Immunol Rev. 2006 Dec;214:229-38
references.pmid: 17100888
references.citation: Nat Rev Cancer. 2008 Apr;8(4):299-308
references.pmid: 18354418
references.citation: J Immunol. 2004 Mar 1;172(5):2731-8
references.pmid: 14978070
references.citation: Stem Cells. 2009 Nov;27(11):2675-85
references.pmid: 19711457
references.citation: J Exp Med. 2005 May 16;201(10):1603-14
references.pmid: 15883170
references.citation: J Cell Physiol. 2009 Nov;221(2):367-77
references.pmid: 19562687
references.citation: J Virol. 2009 Nov;83(21):11188-95
references.pmid: 19692460
references.citation: Mol Ther. 2010 Apr;18(4):843-51
references.pmid: 20179677
references.citation: Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10716-21
references.pmid: 11535826
references.citation: Blood. 2008 Aug 1;112(3):461-9
references.pmid: 18650461
references.citation: Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3360-5
references.pmid: 19211796
references.citation: Adv Immunol. 2009;101:27-79
references.pmid: 19231592
references.citation: J Exp Med. 2005 Mar 7;201(5):805-16
references.pmid: 15738052
references.citation: Blood. 2005 Sep 1;106(5):1601-3
references.pmid: 15914555
references.citation: Science. 2002 Mar 15;295(5562):2097-100
references.pmid: 11896281
references.citation: J Immunol. 2005 Oct 15;175(8):5095-103
references.pmid: 16210613
references.citation: J Immunother. 2008 Oct;31(8):742-51
references.pmid: 18779745
references.citation: Blood. 2005 Jan 15;105(2):617-26
references.pmid: 15374881
references.citation: Nat Rev Immunol. 2005 Dec;5(12):928-40
references.pmid: 16322746
references.citation: Nat Rev Immunol. 2005 Nov;5(11):835-43
references.pmid: 16239902
references.citation: Blood. 2005 Feb 15;105(4):1431-9
references.pmid: 15494433
references.citation: Immunity. 2008 Dec 19;29(6):835-8
references.pmid: 19100694
references.citation: J Clin Invest. 2009 Sep;119(9):2818-29
references.pmid: 19726877
references.citation: Transplantation. 2004 Oct 15;78(7):1081-5
references.pmid: 15480179
references.citation: Nat Rev Immunol. 2007 May;7(5):329-39
references.pmid: 17438573
references.citation: Nat Protoc. 2010 Apr;5(4):811-20
references.pmid: 20360773
references.citation: Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):15768-73
references.pmid: 19720998
references.citation: Cell Stem Cell. 2008 May 8;2(5):422-33
references.pmid: 18462693
references.citation: Blood. 2009 Dec 24;114(27):5473-80
references.pmid: 19797525
references.citation: Blood. 2010 Feb 18;115(7):1354-63
references.pmid: 20008788
references.citation: Curr Opin Immunol. 2003 Jun;15(3):308-14
references.pmid: 12787756
references.citation: Exp Hematol. 2004 Oct;32(10):1000-9
references.pmid: 15504555
references.citation: Blood. 2010 May 20;115(20):4039-42
references.pmid: 20233975
references.citation: Blood. 2009 Oct 22;114(17):3513-23
references.pmid: 19652198
references.citation: Nat Rev Immunol. 2010 May;10(5):317-27
references.pmid: 20414205
references.citation: Cell Stem Cell. 2008 Jul 3;3(1):85-98
references.pmid: 18593561
references.citation: Nat Med. 2010 May;16(5):565-70, 1p following 570
references.pmid: 20400962
references.citation: Cell Stem Cell. 2009 Feb 6;4(2):141-54
references.pmid: 19200803
references.citation: Immunol Rev. 2008 Aug;224:85-97
references.pmid: 18759922
references.citation: Clin Cancer Res. 2007 Apr 1;13(7):2100-8
references.pmid: 17404092
references.citation: Blood. 2008 Oct 1;112(7):2730-7
references.pmid: 18621931
references.citation: Stem Cells. 2009 Mar;27(3):559-67
references.pmid: 19259936
references.citation: Mol Ther. 2010 Apr;18(4):666-8
references.pmid: 20357779
references.citation: Blood. 2005 Apr 15;105(8):3051-7
references.pmid: 15632206
references.citation: Stem Cells. 2007 Nov;25(11):2919-27
references.pmid: 17673526
references.citation: Blood. 2006 Mar 1;107(5):2180-3
references.pmid: 16278307
references.citation: Mol Ther. 2003 Feb;7(2):281-7
references.pmid: 12597917
references.citation: Stem Cells. 2006 May;24(5):1370-80
references.pmid: 16456127
references.citation: J Clin Invest. 2001 Jan;107(2):199-206
references.pmid: 11160136
references.citation: J Immunol. 2009 Jun 1;182(11):6879-88
references.pmid: 19454684
references.citation: Blood. 2010 Mar 25;115(12):2553-4
references.pmid: 20339107
references.citation: Science. 2007 Dec 21;318(5858):1917-20
references.pmid: 18029452
references.citation: Nature. 2009 Sep 3;461(7260):86-90
references.pmid: 19672241
references.citation: Ann N Y Acad Sci. 2009 Sep;1176:219-27
references.pmid: 19796250