Please wait a minute...
Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front. Med.    2018, Vol. 12 Issue (4) : 440-450    https://doi.org/10.1007/s11684-018-0653-9
REVIEW |
Challenges of NK cell-based immunotherapy in the new era
Fang Fang1, Weihua Xiao1(), Zhigang Tian1()
1. Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Signaling Network, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei 230027, China
2. Hefei National Laboratory for Physical Sciences at Microscale, Hefei 230027, China
 Download: PDF(221 KB)   HTML
 Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks
Abstract

Natural killer cells (NKs) have a great potential for cancer immunotherapy because they can rapidly and directly kill transformed cells in the absence of antigen presensitization. Various cellular sources, including peripheral blood mononuclear cells (PBMCs), stem cells, and NK cell lines, have been used for producing NK cells. In particular, NK cells that expanded from allogeneic PBMCs exhibit better efficacy than those that did not. However, considering the safety, activities, and reliability of the cell products, researchers must develop an optimal protocol for producing NK cells from PBMCs in the manufacture setting and clinical therapeutic regimen. In this review, the challenges on NK cell-based therapeutic approaches and clinical outcomes are discussed.

Keywords natural killer cells      immunotherapy      adoptive transfer      genetic modification      immune checkpoint inhibitor     
Corresponding Authors: Weihua Xiao,Zhigang Tian   
Just Accepted Date: 10 July 2018   Online First Date: 26 July 2018    Issue Date: 03 September 2018
 Cite this article:   
Fang Fang,Weihua Xiao,Zhigang Tian. Challenges of NK cell-based immunotherapy in the new era[J]. Front. Med., 2018, 12(4): 440-450.
 URL:  
http://academic.hep.com.cn/fmd/EN/10.1007/s11684-018-0653-9
http://academic.hep.com.cn/fmd/EN/Y2018/V12/I4/440
Fig.1  Killing mechanisms of NK cell against tumor cells. Upon the formation of immunological synapse between activated NK cell and tumor cell, multiple killing mechanisms can be triggered, including direct killing of the tumor cell by the (A) release of granules containing perforin and granzymes and (B) induction of apoptosis through the ligation of Fas-FasL or TRAIL-TRAIL ligand, and indirect killing through (C) the secretion of factors that recruit and promote the activation of other inflammatory cells that indirectly kill a target cell.
Starting material Protocol features NK cell purity Expansion fold Properties References
NK92 Cytokine N/A N/A Additional irradiate step before use [81,103]
CB-MNC Allogeneic feeder cells 72%–95% 35–2389 [104,105]
Stem cell Cytokines and antibodies ≥70% 1000–2100 Lack in vivo “education” [106111]
PBMC CD3 depleted or/and CD56 enriched Cytokine combination 75%–99% 3–131 Additional purification step, low expansion rate [79,112115]
Allogeneic feeder cells plus cytokine or/and antibody ≥90% 16–3637 [116120]
PBMC Cytokines, antibodies, or/and other stimulators ≥70% 140–5712 Simple protocols of expansion, low purity [19,20,121]
Feeder cells 66%–99% 20–14 116 [21,22,122,123]
Tab.1  Manufacture of NK cells
Source of NK cells Patient characteristic Clinical outcome References
NK-92 Solid tumor (n = 31) CR= 0, PR= 4/31, SD= 5/31 [81,124,125]
Lymphoma (n = 3) CR= 1/3, PR= 1/3, SD= 0 [81,124]
Hematopoietic malignancy (n = 12) CR= 1/12, PR= 1/12, SD= 2/12 [103,124]
CD34+ cell-derived NK cells Hematopoietic malignancy, reached CR in previous therapy (n = 18) DFS≥12 months, 1-year OS 11/15, 2-year OS 4/15 [62,73,126]
Hematopoietic malignancy (NK cell combination therapy) (n = 20) CR= 9/20, PR= 9/20, SD= 0 [73,126]
Autologous PBNK Solid tumor (n = 36) CR= 0, PR= 1/36, SD= 10/36 [122,127,128]
Hematopoietic malignancy (n = 9) CR= 0, PR= 2/9, SD= 3/9 [129,130]
Allogeneic PBNK Solid tumor (n = 58) CR= 0, PR= 12/58, SD= 31/58 [78,79,128,131]
Lymphoma (n = 6) CR= 2/6, PR= 2/6, SD= 0 [55]
Hematopoietic malignancy, reached CR in previous therapy (n = 16) DFS≥18 months, 1-year OS 13/16, 2-year OS 12/16 [63,64]
Hematopoietic malignancy (n = 24) CR= 10/24, PR= 1/24, SD= 0 [58,64,132]
Tab.2  Clinical outcome of NK cell-based immunotherapy
1 Herberman RB, Nunn ME, Lavrin DH. Natural cytotoxic reactivity of mouse lymphoid cells against syngeneic acid allogeneic tumors. I. Distribution of reactivity and specificity. Int J Cancer 1975; 16(2): 216–229
https://doi.org/10.1002/ijc.2910160204 pmid: 50294
2 Kiessling R, Klein E, Pross H, Wigzell H. “Natural” killer cells in the mouse. II. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Characteristics of the killer cell. Eur J Immunol 1975; 5(2): 117–121
https://doi.org/10.1002/eji.1830050209 pmid: 1086218
3 Béziat V, Hilton HG, Norman PJ, Traherne JA. Deciphering the killer-cell immunoglobulin-like receptor system at super-resolution for natural killer and T-cell biology. Immunology 2017; 150(3): 248–264
https://doi.org/10.1111/imm.12684 pmid: 27779741
4 Martinet L, Smyth MJ. Balancing natural killer cell activation through paired receptors. Nat Rev Immunol 2015; 15(4): 243–254
https://doi.org/10.1038/nri3799 pmid: 25743219
5 Chester C, Fritsch K, Kohrt HE. Natural killer cell immunomodulation: targeting activating, inhibitory, and co-stimulatory receptor signaling for cancer immunotherapy. Front Immunol 2015; 6: 601
https://doi.org/10.3389/fimmu.2015.00601 pmid: 26697006
6 He Y, Tian Z. NK cell education via nonclassical MHC and non-MHC ligands. Cell Mol Immunol 2017; 14(4): 321–330
https://doi.org/10.1038/cmi.2016.26 pmid: 27264685
7 Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S. Functions of natural killer cells. Nat Immunol 2008; 9(5): 503–510
https://doi.org/10.1038/ni1582 pmid: 18425107
8 Liu Y, Zheng J, Liu Y, Wen L, Huang L, Xiang Z, Lam KT, Lv A, Mao H, Lau YL, Tu W. Uncompromised NK cell activation is essential for virus-specific CTL activity during acute influenza virus infection. Cell Mol Immunol 2017;14: 1–11
pmid: 28413216
9 Sun JC, Lanier LL. NK cell development, homeostasis and function: parallels with CD8+ T cells. Nat Rev Immunol 2011; 11(10): 645–657
https://doi.org/10.1038/nri3044 pmid: 21869816
10 Nair S, Dhodapkar MV. Natural killer T cells in cancer immunotherapy. Front Immunol 2017; 8: 1178
https://doi.org/10.3389/fimmu.2017.01178 pmid: 29018445
11 Shissler SC, Bollino DR, Tiper IV, Bates JP, Derakhshandeh R, Webb TJ. Immunotherapeutic strategies targeting natural killer T cell responses in cancer. Immunogenetics 2016; 68(8): 623–638
https://doi.org/10.1007/s00251-016-0928-8 pmid: 27393665
12 Davis ZB, Felices M, Verneris MR, Miller JS. Natural killer cell adoptive transfer therapy: exploiting the first line of defense against cancer. Cancer J 2015; 21(6): 486–491
https://doi.org/10.1097/PPO.0000000000000156 pmid: 26588681
13 Zhang QF, Yin WW, Xia Y, Yi YY, He QF, Wang X, Ren H, Zhang DZ. Liver-infiltrating CD11b-CD27− NK subsets account for NK-cell dysfunction in patients with hepatocellular carcinoma and are associated with tumor progression. Cell Mol Immunol 2017; 14(10): 819–829
https://doi.org/10.1038/cmi.2016.28 pmid: 27321064
14 Krneta T, Gillgrass A, Chew M, Ashkar AA. The breast tumor microenvironment alters the phenotype and function of natural killer cells. Cell Mol Immunol 2016; 13(5): 628–639
https://doi.org/10.1038/cmi.2015.42 pmid: 26277898
15 Lim O, Jung MY, Hwang YK, Shin EC. Present and future of allogeneic natural killer cell therapy. Front Immunol 2015; 6: 286
https://doi.org/10.3389/fimmu.2015.00286 pmid: 26089823
16 Morvan M, David G, Sébille V, Perrin A, Gagne K, Willem C, Kerdudou N, Denis L, Clémenceau B, Folléa G, Bignon JD, Retière C. Autologous and allogeneic HLA KIR ligand environments and activating KIR control KIR NK-cell functions. Eur J Immunol 2008; 38(12): 3474–3486
https://doi.org/10.1002/eji.200838407 pmid: 19016529
17 Wang W, Erbe AK, DeSantes KB, Sondel PM. Donor selection for ex vivo-expanded natural killer cells as adoptive cancer immunotherapy. Future Oncol 2017; 13(12): 1043–1047
https://doi.org/10.2217/fon-2017-0039 pmid: 28492088
18 Koehl U, Kalberer C, Spanholtz J, Lee DA, Miller JS, Cooley S, Lowdell M, Uharek L, Klingemann H, Curti A, Leung W, Alici E. Advances in clinical NK cell studies: donor selection, manufacturing and quality control. OncoImmunology 2016; 5(4): e1115178
https://doi.org/10.1080/2162402X.2015.1115178 pmid: 27141397
19 Deng X, Terunuma H, Nieda M, Xiao W, Nicol A. Synergistic cytotoxicity of ex vivo expanded natural killer cells in combination with monoclonal antibody drugs against cancer cells. Int Immunopharmacol 2012; 14(4): 593–605
https://doi.org/10.1016/j.intimp.2012.09.014 pmid: 23063974
20 Li X, He C, Liu C, Ma J, Ma P, Cui H, Tao H, Gao B. Expansion of NK cells from PBMCs using immobilized 4-1BBL and interleukin-21. Int J Oncol 2015; 47(1): 335–342
https://doi.org/10.3892/ijo.2015.3005 pmid: 25975533
21 Denman CJ, Senyukov VV, Somanchi SS, Phatarpekar PV, Kopp LM, Johnson JL, Singh H, Hurton L, Maiti SN, Huls MH, Champlin RE, Cooper LJ, Lee DA. Membrane-bound IL-21 promotes sustained ex vivo proliferation of human natural killer cells. PLoS One 2012; 7(1): e30264
https://doi.org/10.1371/journal.pone.0030264 pmid: 22279576
22 Garg TK, Szmania SM, Khan JA, Hoering A, Malbrough PA, Moreno-Bost A, Greenway AD, Lingo JD, Li X, Yaccoby S, Suva LJ, Storrie B, Tricot G, Campana D, Shaughnessy JD Jr, Nair BP, Bellamy WT, Epstein J, Barlogie B, van Rhee F. Highly activated and expanded natural killer cells for multiple myeloma immunotherapy. Haematologica 2012; 97(9): 1348–1356
https://doi.org/10.3324/haematol.2011.056747 pmid: 22419581
23 Schmidt-Wolf IGH, Lefterova P, Johnston V, Huhn D, Blume KG, Negrin RS. Propagation of large numbers of T cells with natural killer cell markers. Br J Haematol 1994; 87(3): 453–458
https://doi.org/10.1111/j.1365-2141.1994.tb08297.x pmid: 7527643
24 Schmidt-Wolf GD, Negrin RS, Schmidt-Wolf IG. Activated T cells and cytokine-induced CD3+CD56+ killer cells. Ann Hematol 1997; 74(2): 51–56
https://doi.org/10.1007/s002770050257 pmid: 9063373
25 Granzin M, Wagner J, Köhl U, Cerwenka A, Huppert V, Ullrich E. Shaping of natural killer cell antitumor activity by ex vivo cultivation. Front Immunol 2017; 8: 458
https://doi.org/10.3389/fimmu.2017.00458 pmid: 28491060
26 Chabannon C, Mfarrej B, Guia S, Ugolini S, Devillier R, Blaise D, Vivier E, Calmels B. Manufacturing natural killer cells as medicinal products. Front Immunol 2016; 7: 504
https://doi.org/10.3389/fimmu.2016.00504 pmid: 27895646
27 Bollino D, Webb TJ. Chimeric antigen receptor-engineered natural killer and natural killer T cells for cancer immunotherapy. Transl Res 2017; 187: 32–43
https://doi.org/10.1016/j.trsl.2017.06.003 pmid: 28651074
28 Song X, Hong SH, Kwon WT, Bailey LM, Basse P, Bartlett DL, Kwon YT, Lee YJ. Secretory trail-armed natural killer cell-based therapy: in vitro and in vivo colorectal peritoneal carcinomatosis xenograft. Mol Cancer Ther 2016; 15(7): 1591–1601
https://doi.org/10.1158/1535-7163.MCT-15-0937 pmid: 27196776
29 Piscopo NJ, Mueller KP, Das A, Hematti P, Murphy WL, Palecek SP, Capitini CM, Saha K. Bioengineering solutions for manufacturing challenges in CAR T cells. Biotechnol J 2018; 13(2): 1700095
pmid: 28840981
30 Hartmann J, Schüßler-Lenz M, Bondanza A, Buchholz CJ. Clinical development of CAR T cells-challenges and opportunities in translating innovative treatment concepts. EMBO Mol Med 2017; 9(9): 1183–1197
https://doi.org/10.15252/emmm.201607485 pmid: 28765140
31 Ritchie DS, Neeson PJ, Khot A, Peinert S, Tai T, Tainton K, Chen K, Shin M, Wall DM, Hönemann D, Gambell P, Westerman DA, Haurat J, Westwood JA, Scott AM, Kravets L, Dickinson M, Trapani JA, Smyth MJ, Darcy PK, Kershaw MH, Prince HM. Persistence and efficacy of second generation CAR T cell against the LeY antigen in acute myeloid leukemia. Mol Ther 2013; 21(11): 2122–2129
https://doi.org/10.1038/mt.2013.154 pmid: 23831595
32 Casucci M, Perna SK, Falcone L, Camisa B, Magnani Z, Bernardi M, Crotta A, Tresoldi C, Fleischhauer K, Ponzoni M, Gregori S, Caligaris Cappio F, Ciceri F, Bordignon C, Cignetti A, Bondanza A, Bonini C. Graft-versus-leukemia effect of HLA-haploidentical central-memory T-cells expanded with leukemic APCs and modified with a suicide gene. Mol Ther 2013; 21(2): 466–475
https://doi.org/10.1038/mt.2012.227 pmid: 23299798
33 Leboeuf C, Mailly L, Wu T, Bour G, Durand S, Brignon N, Ferrand C, Borg C, Tiberghien P, Thimme R, Pessaux P, Marescaux J, Baumert TF, Robinet E. In vivo proof of concept of adoptive immunotherapy for hepatocellular carcinoma using allogeneic suicide gene-modified killer cells. Mol Ther 2014; 22(3): 634–644
https://doi.org/10.1038/mt.2013.277 pmid: 24445938
34 Kailayangiri S, Altvater B, Spurny C, Jamitzky S, Schelhaas S, Jacobs AH, Wiek C, Roellecke K, Hanenberg H, Hartmann W, Wiendl H, Pankratz S, Meltzer J, Farwick N, Greune L, Fluegge M, Rossig C. Targeting Ewing sarcoma with activated and GD2-specific chimeric antigen receptor-engineered human NK cells induces upregulation of immune-inhibitory HLA-G. OncoImmunology 2017; 6(1): e1250050
https://doi.org/10.1080/2162402X.2016.1250050 pmid: 28197367
35 Hu Y, Tian ZG, Zhang C. Chimeric antigen receptor (CAR)-transduced natural killer cells in tumor immunotherapy. Acta Pharmacol Sin 2018; 39(2): 167–176
pmid: 28880014
36 Xu-Monette ZY, Zhang M, Li J, Young KH. PD-1/PD-L1 blockade: have we found the key to unleash the antitumor immune response? Front Immunol 2017; 8: 1597
https://doi.org/10.3389/fimmu.2017.01597 pmid: 29255458
37 Bengsch F, Knoblock DM, Liu A, McAllister F, Beatty GL. CTLA-4/CD80 pathway regulates T cell infiltration into pancreatic cancer. Cancer Immunol Immunother 2017; 66(12): 1609–1617
https://doi.org/10.1007/s00262-017-2053-4 pmid: 28856392
38 Li Y, Li D, Du M. TIM-3: a crucial regulator of NK cells in pregnancy. Cell Mol Immunol 2017; 14:948–950
https://doi.org/10.1038/cmi.2017.85 pmid: 28890545
39 Felices M, Miller JS. Targeting KIR blockade in multiple myeloma: trouble in checkpoint paradise? Clin Cancer Res 2016; 22(21): 5161–5163
https://doi.org/10.1158/1078-0432.CCR-16-1582 pmid: 27430580
40 Guillerey C, Huntington ND, Smyth MJ. Targeting natural killer cells in cancer immunotherapy. Nat Immunol 2016; 17(9): 1025–1036
https://doi.org/10.1038/ni.3518 pmid: 27540992
41 McWilliams EM, Mele JM, Cheney C, Timmerman EA, Fiazuddin F, Strattan EJ, Mo X, Byrd JC, Muthusamy N, Awan FT. Therapeutic CD94/NKG2A blockade improves natural killer cell dysfunction in chronic lymphocytic leukemia. OncoImmunology 2016; 5(10): e1226720
https://doi.org/10.1080/2162402X.2016.1226720 pmid: 27853650
42 Gallois A, Silva I, Osman I, Bhardwaj N. Reversal of natural killer cell exhaustion by TIM-3 blockade. OncoImmunology 2015; 3(12): e946365
https://doi.org/10.4161/21624011.2014.946365 pmid: 25964857
43 Vego H, Sand KL, Høglund RA, Fallang LE, Gundersen G, Holmøy T, Maghazachi AA. Monomethyl fumarate augments NK cell lysis of tumor cells through degranulation and the upregulation of NKp46 and CD107a. Cell Mol Immunol 2016; 13(1): 57–64
https://doi.org/10.1038/cmi.2014.114 pmid: 25435072
44 Floros T, Tarhini AA. Anticancer cytokines: biology and clinical effects of interferon-α2, interleukin (IL)-2, IL-15, IL-21, and IL-12. Semin Oncol 2015; 42(4): 539–548
https://doi.org/10.1053/j.seminoncol.2015.05.015 pmid: 26320059
45 Nielsen CM, Wolf AS, Goodier MR, Riley EM. Synergy between common g chain family cytokines and IL-18 potentiates innate and adaptive pathways of NK cell activation. Front Immunol 2016; 7: 101
https://doi.org/10.3389/fimmu.2016.00101 pmid: 27047490
46 Srivastava S, Pelloso D, Feng H, Voiles L, Lewis D, Haskova Z, Whitacre M, Trulli S, Chen YJ, Toso J, Jonak ZL, Chang HC, Robertson MJ. Effects of interleukin-18 on natural killer cells: costimulation of activation through Fc receptors for immunoglobulin. Cancer Immunol Immunother 2013; 62(6): 1073–1082
https://doi.org/10.1007/s00262-013-1403-0 pmid: 23604103
47 Terme M, Ullrich E, Aymeric L, Meinhardt K, Coudert JD, Desbois M, Ghiringhelli F, Viaud S, Ryffel B, Yagita H, Chen L, Mécheri S, Kaplanski G, Prévost-Blondel A, Kato M, Schultze JL, Tartour E, Kroemer G, Degli-Esposti M, Chaput N, Zitvogel L. Cancer-induced immunosuppression: IL-18-elicited immunoablative NK cells. Cancer Res 2012; 72(11): 2757–2767
https://doi.org/10.1158/0008-5472.CAN-11-3379 pmid: 22427351
48 Wu D, Wu P, Qiu F, Wei Q, Huang J. Human gdT-cell subsets and their involvement in tumor immunity. Cell Mol Immunol 2017; 14(3): 245–253
https://doi.org/10.1038/cmi.2016.55 pmid: 27890919
49 Pittari G, Filippini P, Gentilcore G, Grivel JC, Rutella S. Revving up natural killer cells and cytokine-induced killer cells against hematological malignancies. Front Immunol 2015; 6: 230
https://doi.org/10.3389/fimmu.2015.00230 pmid: 26029215
50 Liu J, Cao X. Cellular and molecular regulation of innate inflammatory responses. Cell Mol Immunol 2016; 13(6): 711–721
https://doi.org/10.1038/cmi.2016.58 pmid: 27818489
51 Mittica G, Capellero S, Genta S, Cagnazzo C, Aglietta M, Sangiolo D, Valabrega G. Adoptive immunotherapy against ovarian cancer. J Ovarian Res 2016; 9(1): 30
https://doi.org/10.1186/s13048-016-0236-9 pmid: 27188274
52 Martín-Antonio B, Suñe G, Perez-Amill L, Castella M, Urbano-Ispizua A. Natural killer cells: angels and devils for immunotherapy. Int J Mol Sci 2017; 18(9): E1868
https://doi.org/10.3390/ijms18091868 pmid: 28850071
53 Fang F, Xiao W, Tian Z. NK cell-based immunotherapy for cancer. Semin Immunol 2017; 31: 37–54
https://doi.org/10.1016/j.smim.2017.07.009 pmid: 28838796
54 Veluchamy JP, Kok N, van der Vliet HJ, Verheul HMW, de Gruijl TD, Spanholtz J. The rise of allogeneic natural killer cells as a platform for cancer immunotherapy: recent innovations and future developments. Front Immunol 2017; 8: 631
https://doi.org/10.3389/fimmu.2017.00631 pmid: 28620386
55 Bachanova V, Burns LJ, McKenna DH, Curtsinger J, Panoskaltsis-Mortari A, Lindgren BR, Cooley S, Weisdorf D, Miller JS. Allogeneic natural killer cells for refractory lymphoma. Cancer Immunol Immunother 2010; 59(11): 1739–1744
https://doi.org/10.1007/s00262-010-0896-z pmid: 20680271
56 Hofer E, Koehl U. Natural Killer cell-based cancer immunotherapies: from immune evasion to promising targeted cellular therapies. Front Immunol 2017; 8: 745
https://doi.org/10.3389/fimmu.2017.00745 pmid: 28747910
57 Pegram HJ, Haynes NM, Smyth MJ, Kershaw MH, Darcy PK. Characterizing the anti-tumor function of adoptively transferred NK cells in vivo. Cancer Immunol Immunother 2010; 59(8): 1235–1246
https://doi.org/10.1007/s00262-010-0848-7 pmid: 20376439
58 Romee R, Rosario M, Berrien-Elliott MM, Wagner JA, Jewell BA, Schappe T, Leong JW, Abdel-Latif S, Schneider SE, Willey S, Neal CC, Yu L, Oh ST, Lee YS, Mulder A, Claas F, Cooper MA, Fehniger TA. Cytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukemia. Sci Transl Med 2016; 8(357): 357ra123
https://doi.org/10.1126/scitranslmed.aaf2341 pmid: 27655849
59 Knorr DA, Bachanova V, Verneris MR, Miller JS. Clinical utility of natural killer cells in cancer therapy and transplantation. Semin Immunol 2014; 26(2): 161–172
https://doi.org/10.1016/j.smim.2014.02.002 pmid: 24618042
60 Dahlberg CI, Sarhan D, Chrobok M, Duru AD, Alici E. Natural killer cell-based therapies targeting cancer: possible strategies to gain and sustain anti-tumor activity. Front Immunol 2015; 6: 605
https://doi.org/10.3389/fimmu.2015.00605 pmid: 26648934
61 Cheng M, Chen Y, Xiao W, Sun R, Tian Z. NK cell-based immunotherapy for malignant diseases. Cell Mol Immunol 2013; 10(3): 230–252
https://doi.org/10.1038/cmi.2013.10 pmid: 23604045
62 Dolstra H, Roeven MWH, Spanholtz J, Hangalapura BN, Tordoir M, Maas F, Leenders M, Bohme F, Kok N, Trilsbeek C, Paardekooper J, van der Waart AB, Westerweel PE, Snijders TJF, Cornelissen JJ, Bos GMJ, Pruijt HFM, De Graaf AO, van der Reijden B, Jansen JH, van der Meer A, Huls G, Cany J, Preijers F, Blijlevens NMA, Schaap NM. Successful transfer of umbilical cord blood CD34+ hematopoietic stem and progenitor-derived NK cells in older acute myeloid leukemia patients. Clin Cancer Res 2017; 23(15):4107–4118
https://doi.org/10.1158/1078-0432.CCR-16-2981
63 Rubnitz JE, Inaba H, Ribeiro RC, Pounds S, Rooney B, Bell T, Pui CH, Leung W. 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(6): 955–959
https://doi.org/10.1200/JCO.2009.24.4590 pmid: 20085940
64 Curti A, Ruggeri L, D’Addio A, Bontadini A, Dan E, Motta MR, Trabanelli S, Giudice V, Urbani E, Martinelli G, Paolini S, Fruet F, Isidori A, Parisi S, Bandini G, Baccarani M, Velardi A, Lemoli RM. Successful transfer of alloreactive haploidentical KIR ligand-mismatched natural killer cells after infusion in elderly high risk acute myeloid leukemia patients. Blood 2011; 118(12): 3273–3279
https://doi.org/10.1182/blood-2011-01-329508 pmid: 21791425
65 Klingemann H, Grodman C, Cutler E, Duque M, Kadidlo D, Klein AK, Sprague KA, Miller KB, Comenzo RL, Kewalramani T, Yu N, Van Etten RA, McKenna DH. Autologous stem cell transplant recipients tolerate haploidentical related-donor natural killer cell-enriched infusions. Transfusion 2013; 53(2): 412–418, quiz 411
https://doi.org/10.1111/j.1537-2995.2012.03764.x pmid: 22738379
66 Kottaridis PD, North J, Tsirogianni M, Marden C, Samuel ER, Jide-Banwo S, Grace S, Lowdell MW. 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(6): e0123416
https://doi.org/10.1371/journal.pone.0123416 pmid: 26062124
67 Bachanova V, Cooley S, Defor TE, Verneris MR, Zhang B, McKenna DH, Curtsinger J, Panoskaltsis-Mortari A, Lewis D, Hippen K, McGlave P, Weisdorf DJ, Blazar BR, Miller JS. Clearance of acute myeloid leukemia by haploidentical natural killer cells is improved using IL-2 diphtheria toxin fusion protein. Blood 2014; 123(25): 3855–3863
https://doi.org/10.1182/blood-2013-10-532531 pmid: 24719405
68 Ciurea SO, Schafer JR, Bassett R, Denman CJ, Cao K, Willis D, Rondon G, Chen J, Soebbing D, Kaur I, Gulbis A, Ahmed S, Rezvani K, Shpall EJ, Lee DA, Champlin RE. Phase 1 clinical trial using mbIL21 ex vivo-expanded donor-derived NK cells after haploidentical transplantation. Blood 2017; 130(16): 1857–1868
https://doi.org/10.1182/blood-2017-05-785659 pmid: 28835441
69 Choi I, Yoon SR, Park SY, Kim H, Jung SJ, Jang YJ, Kang M, Yeom YI, Lee JL, Kim DY, Lee YS, Kang YA, Jeon M, Seol M, Lee JH, Lee JH, Kim HJ, Yun SC, Lee KH. Donor-derived natural killer cells infused after human leukocyte antigen-haploidentical hematopoietic cell transplantation: a dose-escalation study. Biol Blood Marrow Transplant 2014; 20(5): 696–704
https://doi.org/10.1016/j.bbmt.2014.01.031 pmid: 24525278
70 Killig M, Friedrichs B, Meisig J, Gentilini C, Blüthgen N, Loddenkemper C, Labopin M, Basara N, Pfrepper C, Niederwieser DW, Uharek L, Romagnani C. Tracking in vivo dynamics of NK cells transferred in patients undergoing stem cell transplantation. Eur J Immunol 2014; 44(9): 2822–2834
https://doi.org/10.1002/eji.201444586 pmid: 24895051
71 Shah N, Li L, McCarty J, Kaur I, Yvon E, Shaim H, Muftuoglu M, Liu E, Orlowski RZ, Cooper L, Lee D, Parmar S, Cao K, Sobieiski C, Saliba R, Hosing C, Ahmed S, Nieto Y, Bashir Q, Patel K, Bollard C, Qazilbash M, Champlin R, Rezvani K, Shpall EJ. Phase I study of cord blood-derived natural killer cells combined with autologous stem cell transplantation in multiple myeloma. Br J Haematol 2017; 177(3): 457–466
https://doi.org/10.1111/bjh.14570 pmid: 28295190
72 Passweg JR, Tichelli A, Meyer-Monard S, Heim D, Stern M, Kühne T, Favre G, Gratwohl A. Purified donor NK-lymphocyte infusion to consolidate engraftment after haploidentical stem cell transplantation. Leukemia 2004; 18(11): 1835–1838
https://doi.org/10.1038/sj.leu.2403524 pmid: 15457184
73 Yoon SR, Lee YS, Yang SH, Ahn KH, Lee JH, Lee JH, Kim DY, Kang YA, Jeon M, Seol M, Ryu SG, Chung JW, Choi I, Lee KH. 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(6): 1038–1046
https://doi.org/10.1038/bmt.2009.304 pmid: 19881555
74 Rizzieri DA, Storms R, Chen DF, Long G, Yang Y, Nikcevich DA, Gasparetto C, Horwitz M, Chute J, Sullivan K, Hennig T, Misra D, Apple C, Baker M, Morris A, Green PG, Hasselblad V, Chao NJ. Natural killer cell-enriched donor lymphocyte infusions from A 3-6/6 HLA matched family member following nonmyeloablative allogeneic stem cell transplantation. Biol Blood Marrow Transplant 2010; 16(8): 1107–1114
https://doi.org/10.1016/j.bbmt.2010.02.018 pmid: 20188202
75 Schmeel LC, Schmeel FC, Coch C, Schmidt-Wolf IG. Cytokine-induced killer (CIK) cells in cancer immunotherapy: report of the international registry on CIK cells (IRCC). J Cancer Res Clin Oncol 2015; 141(5): 839–849
https://doi.org/10.1007/s00432-014-1864-3 pmid: 25381063
76 Hölsken O, Miller M, Cerwenka A. Exploiting natural killer cells for therapy of melanoma. J Dtsch Dermatol Ges 2015; 13(1): 23–29
https://doi.org/10.1111/ddg.12557 pmid: 25640488
77 Braumüller H, Wieder T, Brenner E, Aßmann S, Hahn M, Alkhaled M, Schilbach K, Essmann F, Kneilling M, Griessinger C, Ranta F, Ullrich S, Mocikat R, Braungart K, Mehra T, Fehrenbacher B, Berdel J, Niessner H, Meier F, van den Broek M, Häring HU, Handgretinger R, Quintanilla-Martinez L, Fend F, Pesic M, Bauer J, Zender L, Schaller M, Schulze-Osthoff K, Röcken M. T-helper-1-cell cytokines drive cancer into senescence. Nature 2013; 494(7437): 361–365
https://doi.org/10.1038/nature11824 pmid: 23376950
78 Geller MA, Cooley S, Judson PL, Ghebre R, Carson LF, Argenta PA, Jonson AL, Panoskaltsis-Mortari A, Curtsinger J, McKenna D, Dusenbery K, Bliss R, Downs LS, Miller JS. A phase II study of allogeneic natural killer cell therapy to treat patients with recurrent ovarian and breast cancer. Cytotherapy 2011; 13(1): 98–107
https://doi.org/10.3109/14653249.2010.515582 pmid: 20849361
79 Iliopoulou EG, Kountourakis P, Karamouzis MV, Doufexis D, Ardavanis A, Baxevanis CN, Rigatos G, Papamichail M, Perez SA. 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(12): 1781–1789
https://doi.org/10.1007/s00262-010-0904-3 pmid: 20703455
80 Yang Y, Lim O, Kim TM, Ahn YO, Choi H, Chung H, Min B, Her JH, Cho SY, Keam B, Lee SH, Kim DW, Hwang YK, Heo DS. Phase I study of random healthy donor-derived allogeneic natural killer cell therapy in patients with malignant lymphoma or advanced solid tumors. Cancer Immunol Res 2016; 4(3): 215–224
https://doi.org/10.1158/2326-6066.CIR-15-0118 pmid: 26787822
81 Tonn T, Schwabe D, Klingemann HG, Becker S, Esser R, Koehl U, Suttorp M, Seifried E, Ottmann OG, Bug G. Treatment of patients with advanced cancer with the natural killer cell line NK-92. Cytotherapy 2013; 15(12): 1563–1570
https://doi.org/10.1016/j.jcyt.2013.06.017 pmid: 24094496
82 Miller JS, Soignier Y, Panoskaltsis-Mortari A, McNearney SA, Yun GH, Fautsch SK, McKenna D, Le C, Defor TE, Burns LJ, Orchard PJ, Blazar BR, Wagner JE, Slungaard A, Weisdorf DJ, Okazaki IJ, McGlave PB. Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood 2005; 105(8): 3051–3057
https://doi.org/10.1182/blood-2004-07-2974 pmid: 15632206
83 Sadozai H, Gruber T, Hunger RE, Schenk M. Recent successes and future directions in immunotherapy of cutaneous melanoma. Front Immunol 2017; 8: 1617
https://doi.org/10.3389/fimmu.2017.01617 pmid: 29276510
84 Overacre-Delgoffe AE, Chikina M, Dadey RE, Yano H, Brunazzi EA, Shayan G, Horne W, Moskovitz JM, Kolls JK, Sander C, Shuai Y, Normolle DP, Kirkwood JM, Ferris RL, Delgoffe GM, Bruno TC, Workman CJ, Vignali DAA. Interferon-g drives Treg fragility to promote anti-tumor immunity. Cell 2017; 169(6): 1130–1141.e11
https://doi.org/10.1016/j.cell.2017.05.005 pmid: 28552348
85 Tallerico R, Garofalo C, Carbone E. A new biological feature of natural killer cells: the recognition of solid tumor-derived cancer stem cells. Front Immunol 2016; 7: 179
https://doi.org/10.3389/fimmu.2016.00179 pmid: 27242786
86 Langers I, Renoux VM, Thiry M, Delvenne P, Jacobs N. Natural killer cells: role in local tumor growth and metastasis. Biologics 2012; 6: 73–82
pmid: 22532775
87 Krasnova Y, Putz EM, Smyth MJ, Souza-Fonseca-Guimaraes F. Bench to bedside: NK cells and control of metastasis. Clin Immunol 2017; 177: 50–59
https://doi.org/10.1016/j.clim.2015.10.001 pmid: 26476139
88 Ames E, Canter RJ, Grossenbacher SK, Mac S, Smith RC, Monjazeb AM, Chen M, Murphy WJ. Enhanced targeting of stem-like solid tumor cells with radiation and natural killer cells. OncoImmunology 2015; 4(9): e1036212
https://doi.org/10.1080/2162402X.2015.1036212 pmid: 26405602
89 Specht HM, Ahrens N, Blankenstein C, Duell T, Fietkau R, Gaipl US, Günther C, Gunther S, Habl G, Hautmann H, Hautmann M, Huber RM, Molls M, Offner R, Rödel C, Rödel F, Schütz M, Combs SE, Multhoff G. Heat shock protein 70 (Hsp70) peptide activated natural killer (NK) cells for the treatment of patients with non-small cell lung cancer (NSCLC) after radiochemotherapy (RCTx) — from preclinical studies to a clinical phase II trial. Front Immunol 2015; 6: 162
https://doi.org/10.3389/fimmu.2015.00162 pmid: 25926832
90 Suck G, Linn YC, Tonn T. Natural killer cells for therapy of leukemia. Transfus Med Hemother 2016; 43(2): 89–95
https://doi.org/10.1159/000445325 pmid: 27226791
91 Li L, Li W, Wang C, Yan X, Wang Y, Niu C, Zhang X, Li M, Tian H, Yao C, Jin H, Han F, Xu D, Han W, Li D, Cui J. Adoptive transfer of natural killer cells in combination with chemotherapy improves outcomes of patients with locally advanced colon carcinoma. Cytotherapy 2018; 20(1): 134–148
https://doi.org/10.1016/j.jcyt.2017.09.009 pmid: 29056549
92 Fine JH, Chen P, Mesci A, Allan DSJ, Gasser S, Raulet DH, Carlyle JR. Chemotherapy-induced genotoxic stress promotes sensitivity to natural killer cell cytotoxicity by enabling missing-self recognition. Cancer Res 2010; 70(18): 7102–7113
https://doi.org/10.1158/0008-5472.CAN-10-1316 pmid: 20823164
93 Dudley ME, Wunderlich JR, Yang JC, Sherry RM, Topalian SL, Restifo NP, Royal RE, Kammula U, White DE, Mavroukakis SA, Rogers LJ, Gracia GJ, Jones SA, Mangiameli DP, Pelletier MM, Gea-Banacloche J, Robinson MR, Berman DM, Filie AC, Abati A, Rosenberg SA. Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J Clin Oncol 2005; 23(10): 2346–2357
https://doi.org/10.1200/JCO.2005.00.240 pmid: 15800326
94 Federico SM, McCarville MB, Shulkin BL, Sondel PM, Hank JA, Hutson P, Meagher M, Shafer A, Ng CY, Leung W, Janssen WE, Wu J, Mao S, Brennan RC, Santana VM, Pappo AS, Furman WL. A pilot trial of humanized anti-GD2 monoclonal antibody (hu14.18K322A) with chemotherapy and natural killer cells in children with recurrent/refractory neuroblastoma. Clin Cancer Res 2017; 23(21): 6441–6449
https://doi.org/10.1158/1078-0432.CCR-17-0379 pmid: 28939747
95 Benson DM Jr, Hofmeister CC, Padmanabhan S, Suvannasankha A, Jagannath S, Abonour R, Bakan C, Andre P, Efebera Y, Tiollier J, Caligiuri MA, Farag SS. A phase 1 trial of the anti-KIR antibody IPH2101 in patients with relapsed/refractory multiple myeloma. Blood 2012; 120(22): 4324–4333
https://doi.org/10.1182/blood-2012-06-438028 pmid: 23033266
96 Sanmamed MF, Pastor F, Rodriguez A, Perez-Gracia JL, Rodriguez-Ruiz ME, Jure-Kunkel M, Melero I. Agonists of co-stimulation in cancer immunotherapy directed against CD137, OX40, GITR, CD27, CD28, and ICOS. Semin Oncol 2015; 42(4): 640–655
https://doi.org/10.1053/j.seminoncol.2015.05.014 pmid: 26320067
97 Anderson AC, Joller N, Kuchroo VK. Lag-3, Tim-3, and TIGIT: co-inhibitory receptors with specialized functions in immune regulation. Immunity 2016; 44(5): 989–1004
https://doi.org/10.1016/j.immuni.2016.05.001 pmid: 27192565
98 Vallera DA, Felice M, McElmurry R, McCullar V, Zhou X, Schmohl JU, Zhang B, Lenvik AJ, Panoskaltsis-Mortari A, Verneris MR, Tolar J, Cooley S, Weisdorf DJ, Blazar BR, Miller JS. IL15 Trispecific killer engagers (TriKE) make natural killer cells specific to CD33+ targets while also inducing persistence, in vivo expansion, and enhanced function. Clin Cancer Res 2016; 22(14):3440–3450
https://doi.org/10.1158/1078-0432.CCR-15-2710 pmid: 26847056
99 Chen S, Li J, Li Q, Wang Z. Bispecific antibodies in cancer immunotherapy. Hum Vaccin Immunother 2016; 12(10): 2491–2500
https://doi.org/10.1080/21645515.2016.1187802 pmid: 27249163
100 Liu D, Tian S, Zhang K, Xiong W, Lubaki NM, Chen Z, Han W. Chimeric antigen receptor (CAR)-modified natural killer cell-based immunotherapy and immunological synapse formation in cancer and HIV. Protein Cell 2017; 8(12): 861–877
https://doi.org/10.1007/s13238-017-0415-5 pmid: 28488245
101 Carlsten M, Childs RW. Genetic manipulation of NK cells for cancer immunotherapy: techniques and clinical implications. Front Immunol 2015; 6: 266
https://doi.org/10.3389/fimmu.2015.00266 pmid: 26113846
102 Sutlu T, Nyström S, Gilljam M, Stellan B, Applequist SE, Alici E. Inhibition of intracellular antiviral defense mechanisms augments lentiviral transduction of human natural killer cells: implications for gene therapy. Hum Gene Ther 2012; 23(10): 1090–1100
https://doi.org/10.1089/hum.2012.080 pmid: 22779406
103 Boyiadzis M, Agha M, Redner RL, Sehgal A, Im A, Hou JZ, Farah R, Dorritie KA, Raptis A, Lim SH, Wang H, Lapteva N, Mei Z, Butterfield LH, Rooney CM, Whiteside TL. Phase 1 clinical trial of adoptive immunotherapy using “off-the-shelf” activated natural killer cells in patients with refractory and relapsed acute myeloid leukemia. Cytotherapy 2017; 19(10): 1225–1232
https://doi.org/10.1016/j.jcyt.2017.07.008 pmid: 28864289
104 Ayello J, Hochberg J, Flower A, Chu Y, Baxi LV, Quish W, van de Ven C, Cairo MS. Genetically re-engineered K562 cells significantly expand and functionally activate cord blood natural killer cells: potential for adoptive cellular immunotherapy. Exp Hematol 2017; 46: 38–47
https://doi.org/10.1016/j.exphem.2016.10.003 pmid: 27765614
105 Shah N, Martin-Antonio B, Yang H, Ku S, Lee DA, Cooper LJ, Decker WK, Li S, Robinson SN, Sekine T, Parmar S, Gribben J, Wang M, Rezvani K, Yvon E, Najjar A, Burks J, Kaur I, Champlin RE, Bollard CM, Shpall EJ. 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(10): e76781
https://doi.org/10.1371/journal.pone.0076781 pmid: 24204673
106 Cany J, van der Waart AB, Tordoir M, Franssen GM, Hangalapura BN, de Vries J, Boerman O, Schaap N, van der Voort R, Spanholtz J, Dolstra H. Natural killer cells generated from cord blood hematopoietic progenitor cells efficiently target bone marrow-residing human leukemia cells in NOD/SCID/IL2Rg(null) mice. PLoS One 2013; 8(6): e64384
https://doi.org/10.1371/journal.pone.0064384 pmid: 23755121
107 Knorr DA, Ni Z, Hermanson D, Hexum MK, Bendzick L, Cooper LJN, Lee DA, Kaufman DS. Clinical-scale derivation of natural killer cells from human pluripotent stem cells for cancer therapy. Stem Cells Transl Med 2013; 2(4): 274–283
https://doi.org/10.5966/sctm.2012-0084 pmid: 23515118
108 Hermanson DL, Bendzick L, Pribyl L, McCullar V, Vogel RI, Miller JS, Geller MA, Kaufman DS. Induced pluripotent stem cell-derived natural killer cells for treatment of ovarian cancer. Stem Cells 2016; 34(1): 93–101
https://doi.org/10.1002/stem.2230 pmid: 26503833
109 Veluchamy JP, Heeren AM, Spanholtz J, van Eendenburg JDH, Heideman DAM, Kenter GG, Verheul HM, van der Vliet HJ, Jordanova ES, de Gruijl TD. High-efficiency lysis of cervical cancer by allogeneic NK cells derived from umbilical cord progenitors is independent of HLA status. Cancer Immunol Immunother 2017; 66(1): 51–61
https://doi.org/10.1007/s00262-016-1919-1 pmid: 27783105
110 Spanholtz J, Preijers F, Tordoir M, Trilsbeek C, Paardekooper J, de Witte T, Schaap N, Dolstra H. 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(6): e20740
https://doi.org/10.1371/journal.pone.0020740 pmid: 21698239
111 Tanaka J, Sugita J, Shiratori S, Shigematu A, Asanuma S, Fujimoto K, Nishio M, Kondo T, Imamura M. Expansion of NK cells from cord blood with antileukemic activity using GMP-compliant substances without feeder cells. Leukemia 2012; 26(5): 1149–1152
https://doi.org/10.1038/leu.2011.345 pmid: 22143670
112 Boerman GH, van Ostaijen-ten Dam MM, Kraal KCJM, Santos SJ, Ball LM, Lankester AC, Schilham MW, Egeler RM, van Tol MJD. Role of NKG2D, DNAM-1 and natural cytotoxicity receptors in cytotoxicity toward rhabdomyosarcoma cell lines mediated by resting and IL-15-activated human natural killer cells. Cancer Immunol Immunother 2015; 64(5): 573–583
https://doi.org/10.1007/s00262-015-1657-9 pmid: 25854581
113 van Ostaijen-ten Dam MM, Prins HJ, Boerman GH, Vervat C, Pende D, Putter H, Lankester A, van Tol MJD, Zwaginga JJ, Schilham MW. Preparation of cytokine-activated NK cells for use in adoptive cell therapy in cancer patients: protocol optimization and therapeutic potential. J Immunother 2016; 39(2): 90–100
https://doi.org/10.1097/CJI.0000000000000110 pmid: 26849078
114 Wendt K, Wilk E, Buyny S, Schmidt RE, Jacobs R. Interleukin-21 differentially affects human natural killer cell subsets. Immunology 2007; 122(4): 486–495
https://doi.org/10.1111/j.1365-2567.2007.02675.x pmid: 17635612
115 Koehl U, Sörensen J, Esser R, Zimmermann S, Grüttner HP, Tonn T, Seidl C, Seifried E, Klingebiel T, Schwabe D. IL-2 activated NK cell immunotherapy of three children after haploidentical stem cell transplantation. Blood Cells Mol Dis 2004; 33(3): 261–266
https://doi.org/10.1016/j.bcmd.2004.08.013 pmid: 15528141
116 Torelli GF, Rozera C, Santodonato L, Peragine N, D’agostino G, Montefiore E, Napolitano MR, Monque DM, Carlei D, Mariglia P, Pauselli S, Gozzer M, Bafti MS, Girelli G, Guarini A, Belardelli F, Foà R. A good manufacturing practice method to ex vivo expand natural killer cells for clinical use. Blood Transfus 2015; 13(3): 464–471
pmid: 25761309
117 Granzin M, Stojanovic A, Miller M, Childs R, Huppert V, Cerwenka A. Highly efficient IL-21 and feeder cell-driven ex vivo expansion of human NK cells with therapeutic activity in a xenograft mouse model of melanoma. OncoImmunology 2016; 5(9): e1219007
https://doi.org/10.1080/2162402X.2016.1219007 pmid: 27757317
118 Kim EK, Ahn YO, Kim S, Kim TM, Keam B, Heo DS .Ex vivo activation and expansion of natural killer cells from patients with advanced cancer with feeder cells from healthy volunteers. Cytotherapy 2013; 15(2): 231–241.e1
https://doi.org/10.1016/j.jcyt.2012.10.019 pmid: 23321334
119 Zhang H, Cui Y, Voong N, Sabatino M, Stroncek DF, Morisot S, Civin CI, Wayne AS, Levine BL, Mackall CL. Activating signals dominate inhibitory signals in CD137L/IL-15 activated natural killer cells. J Immunother 2011; 34(2): 187–195
https://doi.org/10.1097/CJI.0b013e31820d2a21 pmid: 21304401
120 Childs RW, Berg M. Bringing natural killer cells to the clinic: ex vivo manipulation. Hematology Am Soc Hematol Educ Program 2013; 2013: 234–246
https://doi.org/10.1182/asheducation-2013.1.234
121 Oyer JL, Igarashi RY, Kulikowski AR, Colosimo DA, Solh MM, Zakari A, Khaled YA, Altomare DA, Copik AJ. Generation of highly cytotoxic natural killer cells for treatment of acute myelogenous leukemia using a feeder-free, particle-based approach. Biol Blood Marrow Transplant 2015; 21(4): 632–639
https://doi.org/10.1016/j.bbmt.2014.12.037 pmid: 25576425
122 Sakamoto N, Ishikawa T, Kokura S, Okayama T, Oka K, Ideno M, Sakai F, Kato A, Tanabe M, Enoki T, Mineno J, Naito Y, Itoh Y, Yoshikawa T. Phase I clinical trial of autologous NK cell therapy using novel expansion method in patients with advanced digestive cancer. J Transl Med 2015; 13(1): 277
https://doi.org/10.1186/s12967-015-0632-8 pmid: 26303618
123 Lapteva N, Durett AG, Sun J, Rollins LA, Huye LL, Fang J, Dandekar V, Mei Z, Jackson K, Vera J, Ando J, Ngo MC, Coustan-Smith E, Campana D, Szmania S, Garg T, Moreno-Bost A, Vanrhee F, Gee AP, Rooney CM. Large-scale ex vivo expansion and characterization of natural killer cells for clinical applications. Cytotherapy 2012; 14(9): 1131–1143
https://doi.org/10.3109/14653249.2012.700767 pmid: 22900959
124 Williams BA, Law AD, Routy B, denHollander N, Gupta V, Wang XH, Chaboureau A, Viswanathan S, Keating A. A phase I trial of NK-92 cells for refractory hematological malignancies relapsing after autologous hematopoietic cell transplantation shows safety and evidence of efficacy. Oncotarget 2017; 8(51): 89256 –89268
https://doi.org/10.18632/oncotarget.19204 pmid: 29179517
125 Arai S, Meagher R, Swearingen M, Myint H, Rich E, Martinson J, Klingemann H. Infusion of the allogeneic cell line NK-92 in patients with advanced renal cell cancer or melanoma: a phase I trial. Cytotherapy 2008; 10(6): 625–632
https://doi.org/10.1080/14653240802301872 pmid: 18836917
126 Shah N, Li L, McCarty J, Kaur I, Yvon E, Shaim H, Muftuoglu M, Liu E, Orlowski RZ, Cooper L, Lee D, Parmar S, Cao K, Sobieiski C, Saliba R, Hosing C, Ahmed S, Nieto Y, Bashir Q, Patel K, Bollard C, Qazilbash M, Champlin R, Rezvani K, Shpall EJ. Phase I study of cord blood-derived natural killer cells combined with autologous stem cell transplantation in multiple myeloma. Br J Haematol 2017; 177(3): 457–466
https://doi.org/10.1111/bjh.14570 pmid: 28295190
127 Parkhurst MR, Riley JP, Dudley ME, Rosenberg SA. 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(19): 6287–6297
https://doi.org/10.1158/1078-0432.CCR-11-1347 pmid: 21844012
128 Liang S, Xu K, Niu L, Wang X, Liang Y, Zhang M, Chen J, Lin M. Comparison of autogeneic and allogeneic natural killer cells immunotherapy on the clinical outcome of recurrent breast cancer. Onco Targets Ther 2017; 10: 4273–4281
https://doi.org/10.2147/OTT.S139986 pmid: 28894383
129 Leivas A, Perez-Martinez A, Blanchard MJ, Martín-Clavero E, Fernández L, Lahuerta JJ, Martinez-Lopez J. Novel treatment strategy with autologous activated and expanded natural killer cells plus anti-myeloma drugs for multiple myeloma. OncoImmunology 2016; 5(12): e1250051
https://doi.org/10.1080/2162402X.2016.1250051 pmid: 28123890
130 Szmania S, Lapteva N, Garg T, Greenway A, Lingo J, Nair B, Stone K, Woods E, Khan J, Stivers J, Panozzo S, Campana D, Bellamy WT, Robbins M, Epstein J, Yaccoby S, Waheed S, Gee A, Cottler-Fox M, Rooney C, Barlogie B, van Rhee F. Ex vivo-expanded natural killer cells demonstrate robust proliferation in vivo in high-risk relapsed multiple myeloma patients. J Immunother 2015; 38(1): 24–36
https://doi.org/10.1097/CJI.0000000000000059 pmid: 25415285
131 Pérez-Martínez A, Fernández L, Valentín J, Martínez-Romera I, Corral MD, Ramírez M, Abad L, Santamaría S, González-Vicent M, Sirvent S, Sevilla J, Vicario JL, de Prada I, Diaz MA. A phase I/II trial of interleukin-15—stimulated natural killer cell infusion after haplo-identical stem cell transplantation for pediatric refractory solid tumors. Cytotherapy 2015; 17(11): 1594–1603
https://doi.org/10.1016/j.jcyt.2015.07.011 pmid: 26341478
132 Shaffer BC, Le Luduec JB, Forlenza C, Jakubowski AA, Perales MA, Young JW, Hsu KC. Phase II study of haploidentical natural killer cell infusion for treatment of relapsed or persistent myeloid malignancies following allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 2016; 22(4): 705–709
https://doi.org/10.1016/j.bbmt.2015.12.028 pmid: 26772158
[1] Chia-Wei Li, Yun-Ju Lai, Jennifer L. Hsu, Mien-Chie Hung. Activation of phagocytosis by immune checkpoint blockade[J]. Front. Med., 2018, 12(4): 473-480.
[2] Min Yu, Zonghai Li. Natural killer cells in hepatocellular carcinoma: current status and perspectives for future immunotherapeutic approaches[J]. Front. Med., 2017, 11(4): 509-521.
[3] Qiang Gao, Yinghong Shi, Xiaoying Wang, Jian Zhou, Shuangjian Qiu, Jia Fan. Translational medicine in hepatocellular carcinoma[J]. Front Med, 2012, 6(2): 122-133.
[4] Min Cheng, Jian Zhang, Wen Jiang, Yongyan Chen, Zhigang Tian. Natural killer cell lines in tumor immunotherapy[J]. Front Med, 2012, 6(1): 56-66.
[5] Qi-De LIN, Li-Hua QIU. Pathogenesis, diagnosis, and treatment of recurrent spontaneous abortion with immune type[J]. Front Med Chin, 2010, 4(3): 275-279.
[6] Hui QIU, Hui ZHANG, Zuohua FENG. 4-1BBL expressed by eukaryotic cells activates immune cells and suppresses the progression of murine tumor[J]. Front Med Chin, 2009, 3(1): 20-25.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed