Mechanisms of NK cell dysfunction in the tumor microenvironment and current clinical approaches to harness NK cell potential for immunotherapy.
CAR
NK cells
cancer immunotherapy
checkpoint inhibitors
Journal
Journal of leukocyte biology
ISSN: 1938-3673
Titre abrégé: J Leukoc Biol
Pays: England
ID NLM: 8405628
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
revised:
03
09
2020
received:
18
02
2020
accepted:
08
09
2020
pubmed:
30
9
2020
medline:
31
8
2021
entrez:
29
9
2020
Statut:
ppublish
Résumé
NK cells are innate immune cells with inherent capabilities in both recognizing and killing cancer cells. NK cell phenotypes and functional alterations are being described with increasing precision among patients harboring various cancer types, emphasizing the critical role that NK cells play in antitumor immune responses. In addition, advances in understanding NK cell biology have improved our knowledge of such alterations, thereby expanding the potential exploitation of NK cells' anticancer capabilities. In this review, we present an overview of (1) the various types of NK cell alterations that may contribute to immune evasion in cancer patients and (2) the various strategies to improve NK cell-based anticancer immunotherapies, including pharmacologic modulation and/or genetic modification.
Identifiants
pubmed: 32991746
doi: 10.1002/JLB.5MR0920-198RR
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1071-1088Informations de copyright
©2020 Society for Leukocyte Biology.
Références
Vivier E, Raulet DH, Moretta A, et al. Innate or adaptive immunity? The example of natural killer cells. Science. 2011;331:44-49.
Vivier E, Artis D, Colonna M, et al. Innate lymphoid cells: 10 years on. Cell. 2018;174:1054-1066.
Morvan MG, Lanier LL. NK cells and cancer: you can teach innate cells new tricks. Nat Rev Cancer. 2016;16:7-19.
Ruggeri L. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science. 2002;295:2097-2100.
Vivier E, Ugolini S, Blaise D, Chabannon C, Brossay L. Targeting natural killer cells and natural killer T cells in cancer. Nat Rev Immunol. 2012;12:239-252.
Childs RW, Carlsten M. Therapeutic approaches to enhance natural killer cell cytotoxicity against cancer: the force awakens. Nat Rev Drug Discov. 2015;14:487-498.
Shimasaki N, Jain A, Campana D. NK cells for cancer immunotherapy. Nat Rev Drug Discov. 2020;19:200-218. https://doi.org/10.1038/s41573-019-0052-1.
Di Vito C, Mikulak J, Zaghi E, Pesce S, Marcenaro E, Mavilio D. NK cells to cure cancer. Semin Immunol. 2019;41:101272.
Miller JS, Soignier Y, Panoskaltsis-Mortari A, et al. Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood. 2005;105:3051-3057.
Sun H, Sun C. The rise of NK cell checkpoints as promising therapeutic targets in cancer immunotherapy. Front Immunol. 2019;10:2354.
Daher M, Rezvani K. Next generation natural killer cells for cancer immunotherapy: the promise of genetic engineering. Curr Opin Immunol. 2018;51:146-153.
Carlsten M, Childs RW. Genetic manipulation of NK cells for cancer immunotherapy: techniques and clinical implications. Front Immunol. 2015;6:266.
Muntasell A, Ochoa MC, Cordeiro L, et al. Targeting NK-cell checkpoints for cancer immunotherapy. Curr Opin Immunol. 2017;45:73-81.
Matosevic S. Viral and nonviral engineering of natural killer cells as emerging adoptive cancer immunotherapies. J Immunol Res. 2018;2018:4054815.
Rezvani K, Rouce R, Liu E, Shpall E. Engineering natural killer cells for cancer immunotherapy. Mol Ther. 2017;25:1769-1781.
Sun H, Huang Q, Huang M, et al. Human CD96 correlates to natural killer cell exhaustion and predicts the prognosis of human hepatocellular carcinoma. Hepatology. 2019;70:168-183.
Platonova S, Cherfils-Vicini J, Damotte D, et al. Profound coordinated alterations of intratumoral NK cell phenotype and function in lung carcinoma. Cancer Res. 2011;71:5412-5422.
Guillerey C, Ferrari De Andrade L, Vuckovic S, et al. Immunosurveillance and therapy of multiple myeloma are CD226 dependent. J Clin Invest. 2015;125:2077-2089.
Loftus RM, Assmann N, Kedia-Mehta N, et al. Amino acid-dependent cMyc expression is essential for NK cell metabolic and functional responses in mice. Nat Commun. 2018;9:2341.
Viel S, Marçais A, Guimaraes FS-F, et al. TGF-β inhibits the activation and functions of NK cells by repressing the mTOR pathway. Sci Signal. 2016;9:ra19.
O'brien KL, Finlay DK. Immunometabolism and natural killer cell responses. Nat Rev Immunol. 2019;19:282-290.
Harmon C, Robinson MW, Hand F, et al. Lactate-mediated acidification of tumor microenvironment induces apoptosis of liver-resident NK cells in colorectal liver metastasis. Cancer Immunol Res. 2019;7:335-346.
Gao Y, Souza-Fonseca-Guimaraes F, Bald T, et al. Tumor immunoevasion by the conversion of effector NK cells into type 1 innate lymphoid cells. Nat Immunol. 2017;18:1004-1015.
Mandal R, Şenbabaoğlu Y, Desrichard A, et al. The head and neck cancer immune landscape and its immunotherapeutic implications. JCI Insight. 2016;1:e89829.
Schleypen JS. Cytotoxic markers and frequency predict functional capacity of natural killer cells infiltrating renal cell carcinoma. Clin Cancer Res. 2006;12:718-725.
Mamessier E, Sylvain A, Thibult M-L, et al. Human breast cancer cells enhance self tolerance by promoting evasion from NK cell antitumor immunity. J Clin Invest. 2011;121:3609-3622.
Fauriat C, Just-Landi S, Mallet Franç, et al. Deficient expression of NCR in NK cells from acute myeloid leukemia: evolution during leukemia treatment and impact of leukemia cells in NCRdull phenotype induction. Blood. 2007;109:323-330.
Sullivan EM, Jeha S, Kang G, et al. NK cell genotype and phenotype at diagnosis of acute lymphoblastic leukemia correlate with postinduction residual disease. Clin Cancer Res. 2014;20:5986-5994.
Le Maux Chansac B, Moretta A, Vergnon I, et al. NK cells infiltrating a MHC class I-deficient lung adenocarcinoma display impaired cytotoxic activity toward autologous tumor cells associated with altered NK cell-triggering receptors. J Immunol. 2005;175:5790-5798.
Peng Y-P, Zhu Yi, Zhang J-J, et al. Comprehensive analysis of the percentage of surface receptors and cytotoxic granules positive natural killer cells in patients with pancreatic cancer, gastric cancer, and colorectal cancer. J Transl Med. 2013;11:262.
Zhang Q-F, Yin W-W, Xia Y, et al. 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;14:819-829.
Stringaris K, Sekine T, Khoder A, et al. Leukemia-induced phenotypic and functional defects in natural killer cells predict failure to achieve remission in acute myeloid leukemia. Haematologica. 2014;99:836-847.
Wu Y, Kuang D-M, Pan W-D, et al. Monocyte/macrophage-elicited natural killer cell dysfunction in hepatocellular carcinoma is mediated by CD48/2B4 interactions. Hepatology. 2013;57:1107-1116.
Garcia-Iglesias T, Del Toro-Arreola A, Albarran-Somoza B, et al. Low NKp30, NKp46 and NKG2D expression and reduced cytotoxic activity on NK cells in cervical cancer and precursor lesions. BMC Cancer. 2009;9:186.
Pasero C, Gravis G, Guerin M, et al. Inherent and tumor-driven immune tolerance in the prostate microenvironment impairs natural killer cell antitumor activity. Cancer Res. 2016;76:2153-2165.
Chretien A-S, Devillier R, Fauriat C, et al. NKp46 expression on NK cells as a prognostic and predictive biomarker for response to allo-SCT in patients with AML. Oncoimmunology. 2017;6:e1307491.
Chretien A-S, Fauriat C, Orlanducci F, et al. NKp30 expression is a prognostic immune biomarker for stratification of patients with intermediate-risk acute myeloid leukemia. Oncotarget. 2017;8:49548-49563.
Semeraro M, Rusakiewicz S, Minard-Colin V, et al. Clinical impact of the NKp30/B7-H6 axis in high-risk neuroblastoma patients. Sci Transl Med. 2015;7:283ra55.
Sanchez-Correa B, Gayoso I, Bergua JM, et al. Decreased expression of DNAM-1 on NK cells from acute myeloid leukemia patients. Immunol Cell Biol. 2012;90:109-115.
Carlsten M, Norell H, Bryceson YT, et al. Primary human tumor cells expressing CD155 impair tumor targeting by down-regulating DNAM-1 on NK cells. J Immunol. 2009;183:4921-4930.
Chiesa MD, Carlomagno S, Frumento G, et al. The tryptophan catabolite L-kynurenine inhibits the surface expression of NKp46- and NKG2D-activating receptors and regulates NK-cell function. Blood. 2006;108:4118-4125.
Ferrari De Andrade L, Tay REn, Pan D, et al. Antibody-mediated inhibition of MICA and MICB shedding promotes NK cell-driven tumor immunity. Science. 2018;359:1537-1542.
Sun C, Xu J, Huang Q, et al. High NKG2A expression contributes to NK cell exhaustion and predicts a poor prognosis of patients with liver cancer. Oncoimmunology. 2017;6:e1264562.
Stanietsky N, Simic H, Arapovic J, et al. The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity. Proc Natl Acad Sci USA. 2009;106:17858-17863.
Sarhan D, Cichocki F, Zhang B, et al. Adaptive NK cells with low TIGIT expression are inherently resistant to myeloid-derived suppressor cells. Cancer Res. 2016;76:5696-5706.
Zhang Q, Bi J, Zheng X, et al. Blockade of the checkpoint receptor TIGIT prevents NK cell exhaustion and elicits potent anti-tumor immunity. Nat Immunol. 2018;19:723-732.
Chretien A-S, Fauriat C, Orlanducci F, et al. Natural killer defective maturation is associated with adverse clinical outcome in patients with acute myeloid leukemia. Front Immunol. 2017;8:573.
Carrega P, Morandi B, Costa R, et al. Natural killer cells infiltrating human nonsmall-cell lung cancer are enriched in CD56 bright CD16(-) cells and display an impaired capability to kill tumor cells. Cancer. 2008;112:863-875.
Romee R, Rosario M, Berrien-Elliott MM, et al. Cytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukemia. Sci Transl Med. 2016;8:357ra123.
Mundy-Bosse BL, Scoville SD, Chen Li, et al. MicroRNA-29b mediates altered innate immune development in acute leukemia. J Clin Invest. 2016;126:4404-4416.
Scoville SD, Nalin AP, Chen L, et al. Human AML activates the aryl hydrocarbon receptor pathway to impair NK cell development and function. Blood. 2018;132:1792-1804.
Young A, Ngiow SF, Gao Y, et al. A2AR adenosine signaling suppresses natural killer cell maturation in the tumor microenvironment. Cancer Res. 2018;78:1003-1016.
Kobayashi T, Mattarollo SR. Natural killer cell metabolism. Mol Immunol. 2019;115:3-11.
Keppel MP, Saucier N, Mah AY, Vogel TP, Cooper MA. Activation-specific metabolic requirements for NK Cell IFN-γ production. J Immunol. 2015;194:1954-1962.
Keating SE, Zaiatz-Bittencourt V, Loftus RM, et al. Metabolic reprogramming supports IFN-γ production by CD56bright NK cells. J Immunol. 2016;196:2552-2560.
Wang Z, Guan Di, Wang S, Chai LYiA, Xu S, Lam K-P. Glycolysis and oxidative phosphorylation play critical roles in natural killer cell receptor-mediated natural killer cell functions. Front Immunol. 2020;11:202.
Donnelly RP, Loftus RM, Keating SE, et al. mTORC1-dependent metabolic reprogramming is a prerequisite for NK cell effector function. J Immunol. 2014;193:4477-4484.
Assmann N, O'brien KL, Donnelly RP, et al. Srebp-controlled glucose metabolism is essential for NK cell functional responses. Nat Immunol. 2017;18:1197-1206.
Marçais A, Cherfils-Vicini J, Viant C, et al. The metabolic checkpoint kinase mTOR is essential for IL-15 signaling during the development and activation of NK cells. Nat Immunol. 2014;15:749-757.
Jensen H, Potempa M, Gotthardt D, Lanier LL. Cutting edge: iL-2-induced expression of the amino acid transporters SLC1A5 and CD98 is a prerequisite for NKG2D-mediated activation of human NK cells. J Immunol. 2017;199:1967-1972.
Cichocki F, Valamehr B, Bjordahl R, et al. GSK3 inhibition drives maturation of NK cells and enhances their antitumor activity. Cancer Res. 2017;77:5664-5675.
Parameswaran R, Ramakrishnan P, Moreton SA, et al. Repression of GSK3 restores NK cell cytotoxicity in AML patients. Nat Commun. 2016;7:11154.
Horton JD, Goldstein JL, Brown MS. SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest. 2002;109:1125-1131.
Tobin LM, Mavinkurve M, Carolan E, et al. NK cells in childhood obesity are activated, metabolically stressed, and functionally deficient. JCI Insight. 2017;2.
Michelet X, Dyck L, Hogan A, et al. Metabolic reprogramming of natural killer cells in obesity limits antitumor responses. Nat Immunol. 2018;19:1330-1340.
Still ER, Yuneva MO. Hopefully devoted to Q: targeting glutamine addiction in cancer. Br J Cancer. 2017;116:1375-1381.
Regis S, Dondero A, Caliendo F, Bottino C, Castriconi R. NK cell function regulation by TGF-β-induced epigenetic mechanisms. Front Immunol. 2020;11:311.
Zaiatz-Bittencourt V, Finlay DK, Gardiner CM. Canonical TGF-β signaling pathway represses human NK cell metabolism. J Immunol. 2018;200:3934-3941.
Cong J, Wang X, Zheng X, et al. Dysfunction of natural killer cells by FBP1-induced inhibition of glycolysis during lung cancer progression. Cell Metab. 2018;28:243-255.e5.
Adams CM, Reitz J, De Brabander JK, et al. Cholesterol and 25-hydroxycholesterol inhibit activation of SREBPs by different mechanisms, both involving SCAP and Insigs. J Biol Chem. 2004;279:52772-52780.
Li Di, Long W, Huang R, Chen Y, Xia M. 27-Hydroxycholesterol inhibits sterol regulatory element-binding protein 1 activation and hepatic lipid accumulation in mice. Obesity (Silver Spring). 2018;26:713-722.
Eibinger G, Fauler G, Bernhart E, et al. On the role of 25-hydroxycholesterol synthesis by glioblastoma cell lines. Implications for chemotactic monocyte recruitment. Exp Cell Res. 2013;319:1828-1838.
Wu Q, Ishikawa T, Sirianni R, et al. 27-Hydroxycholesterol promotes cell-autonomous, ER-positive breast cancer growth. Cell Rep. 2013;5:637-645.
Cortez VS, Ulland TK, Cervantes-Barragan L, et al. SMAD4 impedes the conversion of NK cells into ILC1-like cells by curtailing non-canonical TGF-β signaling. Nat Immunol. 2017;18:995-1003.
Hawke LG, Mitchell BZ, Ormiston ML. TGF-β and IL-15 synergize through MAPK pathways to drive the conversion of human NK cells to an innate lymphoid cell 1-like phenotype. J Immunol. 2020;204:3171-3181. https://doi.org/10.4049/jimmunol.1900866.
Vacca P, Vitale C, Munari E, Cassatella MA, Mingari MC, Moretta L. Human innate lymphoid cells: their functional and cellular interactions in decidua. Front Immunol. 2018;9:1897.
Jabrane-Ferrat N. Features of human decidual NK cells in healthy pregnancy and during viral infection. Front Immunol. 2019;10:1397.
Castagna L, Mavilio D. Re-discovering NK cell allo-reactivity in the therapy of solid tumors. J Immunother Cancer. 2016;4:54.
Sakamoto N, Ishikawa T, Kokura S, et al. Phase I clinical trial of autologous NK cell therapy using novel expansion method in patients with advanced digestive cancer. J Transl Med. 2015;13:277.
Burns LJ, Weisdorf DJ, Defor TE, et al. IL-2-based immunotherapy after autologous transplantation for lymphoma and breast cancer induces immune activation and cytokine release: a phase I/II trial. Bone Marrow Transplant. 2003;32:177-186.
Shaffer BC, Le Luduec J-B, Forlenza C, et al. 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;22:705-709.
Curti A, Ruggeri L, D'addio A, 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;118:3273-3279.
Björklund AT, Carlsten M, Sohlberg E, et al. Complete remission with reduction of high-risk clones following haploidentical NK cell therapy against MDS and AML. Clin Cancer Res. 2018;24:1834-1844. https://doi.org/10.1158/1078-0432.CCR-17-3196.
Rubnitz JE, Inaba H, Ribeiro RC, et al. 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;28:955-959.
Nguyen R, Wu H, Pounds S, et al. A phase II clinical trial of adoptive transfer of haploidentical natural killer cells for consolidation therapy of pediatric acute myeloid leukemia. J Immunother Cancer. 2019;7:81.
Bachanova V, Cooley S, Defor TE, et al. Clearance of acute myeloid leukemia by haploidentical natural killer cells is improved using IL-2 diphtheria toxin fusion protein. Blood. 2014;123:3855-3863.
Cooley S, He F, Bachanova V, et al. First-in-human trial of rhIL-15 and haploidentical natural killer cell therapy for advanced acute myeloid leukemia. Blood Adv. 2019;3:1970-1980.
Szmania S, Lapteva N, Garg T, 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.
Bachanova V, Sarhan D, Defor TE, et al. Haploidentical natural killer cells induce remissions in non-Hodgkin lymphoma patients with low levels of immune-suppressor cells. Cancer Immunol Immunother. 2018;67:483-494.
Geller MA, Cooley S, Judson PL, 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.
Federico SM, Mccarville MB, Shulkin BL, et al. 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;23:6441-6449.
Modak S, Le Luduec J-B, Cheung IY, et al. Adoptive immunotherapy with haploidentical natural killer cells and Anti-GD2 monoclonal antibody m3F8 for resistant neuroblastoma: results of a phase I study. Oncoimmunology. 2018;7:e1461305.
Cooley S, Parham P, Miller JS. Strategies to activate NK cells to prevent relapse and induce remission following hematopoietic stem cell transplantation. Blood. 2018;131:1053-1062.
Stern M, Passweg JR, Meyer-Monard S, 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;48:433-438.
Passweg JR, Tichelli A, Meyer-Monard S, et al. Purified donor NK-lymphocyte infusion to consolidate engraftment after haploidentical stem cell transplantation. Leukemia. 2004;18:1835-1838.
Rizzieri DA, Storms R, Chen D-F, et al. 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;16:1107-1114.
Ciurea SO, Schafer JR, Bassett R, et al. Phase 1 clinical trial using mbIL21 ex vivo-expanded donor-derived NK cells after haploidentical transplantation. Blood. 2017;130:1857-1868.
Groth A, Klöss S, Pogge Von Strandmann E, Koehl U, Koch J. Mechanisms of tumor and viral immune escape from natural killer cell-mediated surveillance. J Innate Immun. 2011;3:344-354.
Ruggeri L, Mancusi A, Burchielli E, et al. NK cell alloreactivity and allogeneic hematopoietic stem cell transplantation. Blood Cells Mol Dis. 2008;40:84-90.
Romagné F, André P, Spee P, et al. Preclinical characterization of 1-7F9, a novel human anti-KIR receptor therapeutic antibody that augments natural killer-mediated killing of tumor cells. Blood. 2009;114:2667-2677.
Benson DM, Bakan CE, Zhang S, et al. IPH2101, a novel anti-inhibitory KIR antibody, and lenalidomide combine to enhance the natural killer cell versus multiple myeloma effect. Blood. 2011;118:6387-6391.
Kohrt HE, Thielens A, Marabelle A, et al. Anti-KIR antibody enhancement of anti-lymphoma activity of natural killer cells as monotherapy and in combination with anti-CD20 antibodies. Blood. 2014;123:678-686.
Vey N, Bourhis J-H, Boissel N, et al. A phase 1 trial of the anti-inhibitory KIR mAb IPH2101 for AML in complete remission. Blood. 2012;120:4317-4323.
Vey N, Karlin L, Sadot-Lebouvier S, et al. A phase 1 study of lirilumab (antibody against killer immunoglobulin-like receptor antibody KIR2D; IPH2102) in patients with solid tumors and hematologic malignancies. Oncotarget. 2018;9:17675-17688.
Benson DM, Hofmeister CC, Padmanabhan S, et al. A phase 1 trial of the anti-KIR antibody IPH2101 in patients with relapsed/refractory multiple myeloma. Blood. 2012;120:4324-4333.
Yalniz FF, Daver N, Rezvani K, et al. A pilot trial of lirilumab with or without azacitidine for patients with myelodysplastic syndrome. Clin Lymphoma Myeloma Leuk. 2018;18:658-663.e2.
Korde N, Carlsten M, Lee M-J, et al. A phase II trial of pan-KIR2D blockade with IPH2101 in smoldering multiple myeloma. Haematologica. 2014;99:e81-e83.
Carlsten M, Korde N, Kotecha R, et al. Checkpoint Inhibition of KIR2D with the Monoclonal Antibody IPH2101 Induces Contraction and Hyporesponsiveness of NK-cells in Patients with Myeloma. Clin Cancer Res. 2016;22:5211-5222. https://doi.org/10.1158/1078-0432.CCR-16-1108.
Ardolino M, Azimi CS, Iannello A, et al. Cytokine therapy reverses NK cell anergy in MHC-deficient tumors. J Clin Invest. 2014;124:4781-4794.
Benson DM, Cohen AD, Jagannath S, et al. A phase i trial of the anti-KIR antibody IPH2101 and lenalidomide in patients with relapsed/refractory multiple myeloma. Clin Cancer Res. 2015;21:4055-4061.
Nijhof IS, Van Bueren JJL, Van Kessel B, et al. Daratumumab-mediated lysis of primary multiple myeloma cells is enhanced in combination with the human anti-KIR antibody IPH2102 and lenalidomide. Haematologica. 2015;100:263-268.
Bagot M, Porcu P, Marie-Cardine A, et al. IPH4102, a first-in-class anti-KIR3DL2 monoclonal antibody, in patients with relapsed or refractory cutaneous T-cell lymphoma: an international, first-in-human, open-label, phase 1 trial. Lancet Oncol. 2019;20:1160-1170.
Braud VM, Allan DSJ, O'callaghan CA, et al. HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C. Nature. 1998;391:795-799.
Meckawy GR, Mohamed AM, Zaki WK, et al. Natural killer NKG2A and NKG2D in patients with colorectal cancer. J Gastrointest Oncol. 2019;10:218-225.
Mcwilliams EM, Mele JM, Cheney C, et al. Therapeutic CD94/NKG2A blockade improves natural killer cell dysfunction in chronic lymphocytic leukemia. Oncoimmunology. 2016;5:e1226720.
Ghasemzadeh M, Hosseini E, Schwarer AP, Pourfathollah AA. NK cell maturation to CD56(dim) subset associated with high levels of NCRs overrides the inhibitory effect of NKG2A and recovers impaired NK cell cytolytic potential after allogeneic hematopoietic stem cell transplantation. Leuk Res. 2016;43:58-65.
Pical-Izard C, Crocchiolo R, Granjeaud S, et al. Reconstitution of natural killer cells in HLA-matched HSCT after reduced-intensity conditioning: impact on clinical outcome. Biol Blood Marrow Transplant. 2015;21:429-439.
Roberto A, Di Vito C, Zaghi E, et al. The early expansion of anergic NKG2Apos/CD56dim/CD16neg natural killer represents a therapeutic target in haploidentical hematopoietic stem cell transplantation. Haematologica. 2018;103:1390-1402.
Russo A, Oliveira G, Berglund S, et al. NK cell recovery after haploidentical HSCT with posttransplant cyclophosphamide: dynamics and clinical implications. Blood. 2018;131:247-262.
Godal R, Bachanova V, Gleason M, et al. Natural killer cell killing of acute myelogenous leukemia and acute lymphoblastic leukemia blasts by killer cell immunoglobulin-like receptor-negative natural killer cells after NKG2A and LIR-1 blockade. Biol Blood Marrow Transplant. 2010;16:612-621.
Ruggeri L, Urbani E, Andre P, et al. Effects of anti-NKG2A antibody administration on leukemia and normal hematopoietic cells. Haematologica. 2016;101:626-633.
André P, Denis C, Soulas C, et al. Anti-NKG2A mAb is a checkpoint inhibitor that promotes anti-tumor immunity by unleashing both T and NK cells. Cell. 2018;175:1731-1743.e13.
Tinker AV, Hirte HW, Provencher D, et al. Dose-ranging and cohort-expansion study of monalizumab (IPH2201) in patients with advanced gynecologic malignancies: a trial of the canadian cancer trials group (CCTG): iND221. Clin Cancer Res. 2019;25:6052-6060.
Anderson AC, Joller N, Kuchroo VK. Lag-3, Tim-3, and TIGIT: co-inhibitory receptors with specialized functions in immune regulation. Immunity. 2016;44:989-1004.
Chiba S, Baghdadi M, Akiba H, et al. Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1. Nat Immunol. 2012;13:832-842.
Huang Yu-H, Zhu C, Kondo Y, et al. CEACAM1 regulates TIM-3-mediated tolerance and exhaustion. Nature. 2015;517:386-390.
Zhu C, Anderson AC, Schubart A, et al. The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity. Nat Immunol. 2005;6:1245-1252.
Anderson AC. Tim-3: an emerging target in the cancer immunotherapy landscape. Cancer Immunol Res. 2014;2:393-398.
Fourcade J, Sun Z, Benallaoua M, et al. Upregulation of Tim-3 and PD-1 expression is associated with tumor antigen-specific CD8+ T cell dysfunction in melanoma patients. J Exp Med. 2010;207:2175-2186.
Sakuishi K, Apetoh L, Sullivan JM, Blazar BR, Kuchroo VK, Anderson AC. Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity. J Exp Med. 2010;207:2187-2194.
Solinas C, De Silva P, Bron D, Willard-Gallo K, Sangiolo D. Significance of TIM3 expression in cancer: from biology to the clinic. Semin Oncol. 2019;46:372-379.
Da Silva IP, Gallois A, Jimenez-Baranda S, et al. Reversal of NK-cell exhaustion in advanced melanoma by Tim-3 blockade. Cancer Immunol Res. 2014;2:410-422.
Li X, Wang Bo, Gu L, et al. Tim-3 expression predicts the abnormal innate immune status and poor prognosis of glioma patients. Clin Chim Acta. 2018;476:178-184.
Wang Z, Zhu J, Gu H, et al. The clinical significance of abnormal Tim-3 expression on NK cells from patients with gastric cancer. Immunol Invest. 2015;44:578-589.
Zheng Y, Li Yu, Lian J, et al. TNF-α-induced Tim-3 expression marks the dysfunction of infiltrating natural killer cells in human esophageal cancer. J Transl Med. 2019;17:165.
Zhang W, Feng H, Chen Q, Lu X, Ge J. The functional potency of natural killer cells in response to IL-2/IL-15/IL-21 stimulation is limited by a concurrent upregulation of Tim-3 in bladder cancer. Exp Cell Res. 2018;372:92-98.
Audenet F, Farkas AM, Anastos H, Galsky MD, Bhardwaj N, Sfakianos JP. Immune phenotype of peripheral blood mononuclear cells in patients with high-risk non-muscle invasive bladder cancer. World J Urol. 2018;36:1741-1748.
Yin M, Di G, Bian M. Dysfunction of natural killer cells mediated by PD-1 and Tim-3 pathway in anaplastic thyroid cancer. Int Immunopharmacol. 2018;64:333-339.
Xu L, Huang Y, Tan L, et al. Increased Tim-3 expression in peripheral NK cells predicts a poorer prognosis and Tim-3 blockade improves NK cell-mediated cytotoxicity in human lung adenocarcinoma. Int Immunopharmacol. 2015;29:635-641.
Gallois A, Silva I, Osman I, Bhardwaj N. Reversal of natural killer cell exhaustion by TIM-3 blockade. Oncoimmunology. 2014;3:e946365.
Koyama S, Akbay EA, Li YY, et al. Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints. Nat Commun. 2016;7:10501.
Gleason MK, Lenvik TR, Mccullar V, et al. Tim-3 is an inducible human natural killer cell receptor that enhances interferon gamma production in response to galectin-9. Blood. 2012;119:3064-3072.
Folgiero V, Cifaldi L, Pira GLi, Goffredo BM, Vinti L, Locatelli F. TIM-3/Gal-9 interaction induces IFNγ-dependent IDO1 expression in acute myeloid leukemia blast cells. J Hematol Oncol. 2015;8:36.
Sabatos-Peyton CA, Nevin J, Brock A, et al. Blockade of Tim-3 binding to phosphatidylserine and CEACAM1 is a shared feature of anti-Tim-3 antibodies that have functional efficacy. Oncoimmunology. 2018;7:e1385690.
Triebel F, Jitsukawa S, Baixeras E, et al. LAG-3, a novel lymphocyte activation gene closely related to CD4. J Exp Med. 1990;171:1393-1405.
Baixeras E, Huard B, Miossec C, et al. Characterization of the lymphocyte activation gene 3-encoded protein. A new ligand for human leukocyte antigen class II antigens. J Exp Med. 1992;176:327-337.
Workman CJ, Cauley LS, Kim In-J, Blackman MA, Woodland DL, Vignali DAA. Lymphocyte activation gene-3 (CD223) regulates the size of the expanding T cell population following antigen activation in vivo. J Immunol. 2004;172:5450-5455.
Workman C J, Vignali D A A. The CD4-related molecule, LAG-3 (CD223), regulates the expansion of activated T cells. Eur J Immunol. 2003;33:970-979.
Wang J, Sanmamed MF, Datar I, et al. Fibrinogen-like Protein 1 Is a Major Immune Inhibitory Ligand of LAG-3. Cell. 2019;176:334-347.e12.e12.
Mishra AK, Kadoishi T, Wang X, et al. Squamous cell carcinomas escape immune surveillance via inducing chronic activation and exhaustion of CD8+ T Cells co-expressing PD-1 and LAG-3 inhibitory receptors. Oncotarget. 2016;7:81341-81356.
Datar I, Sanmamed MF, Wang J, et al. Expression analysis and significance of PD-1, LAG-3, and TIM-3 in human non-small cell lung cancer using spatially resolved and multiparametric single-cell analysis. Clin Cancer Res. 2019;25:4663-4673.
Miyazaki T, Dierich A, Benoist C, Mathis D. Independent modes of natural killing distinguished in mice lacking Lag3. Science. 1996;272:405-408.
Martinet L, Smyth MJ. Balancing natural killer cell activation through paired receptors. Nat Rev Immunol. 2015;15:243-254.
Stanietsky N, Rovis TL, Glasner A, et al. Mouse TIGIT inhibits NK-cell cytotoxicity upon interaction with PVR. Eur J Immunol. 2013;43:2138-2150.
Liu S, Zhang H, Li M, et al. Recruitment of Grb2 and SHIP1 by the ITT-like motif of TIGIT suppresses granule polarization and cytotoxicity of NK cells. Cell Death Differ. 2013;20:456-464.
Chan CJ, Martinet L, Gilfillan S, et al. The receptors CD96 and CD226 oppose each other in the regulation of natural killer cell functions. Nat Immunol. 2014;15:431-438.
Blake SJ, Dougall WC, Miles JJ, Teng MWL, Smyth MJ. Molecular pathways: targeting CD96 and TIGIT for cancer immunotherapy. Clin Cancer Res. 2016;22:5183-5188.
Blake SJ, Stannard K, Liu J, et al. Suppression of metastases using a new lymphocyte checkpoint target for cancer immunotherapy. Cancer Discov. 2016;6:446-459.
Felices M, Lenvik TR, Davis ZB, Miller JS, Vallera DA. Generation of BiKEs and TriKEs to improve NK cell-mediated targeting of tumor cells. Methods Mol Biol. 2016;1441:333-346.
Kellner C, Bruenke J, Horner H, et al. Heterodimeric bispecific antibody-derivatives against CD19 and CD16 induce effective antibody-dependent cellular cytotoxicity against B-lymphoid tumor cells. Cancer Lett. 2011;303:128-139.
Bruenke J, Barbin K, Kunert S, et al. Effective lysis of lymphoma cells with a stabilised bispecific single-chain Fv antibody against CD19 and FcgammaRIII (CD16). Br J Haematol. 2005;130:218-228.
Wu J, Fu J, Zhang M, Liu D. AFM13: a first-in-class tetravalent bispecific anti-CD30/CD16A antibody for NK cell-mediated immunotherapy. J Hematol Oncol. 2015;8:96.
Pahl JHW, Koch J, Götz J-J, et al. CD16A activation of NK cells promotes NK cell proliferation and memory-like cytotoxicity against cancer cells. Cancer Immunol Res. 2018;6:517-527.
Rothe A, Sasse S, Topp MS, et al. A phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13 in patients with relapsed or refractory Hodgkin lymphoma. Blood. 2015;125:4024-4031.
Gleason MK, Ross JA, Warlick ED, et al. CD16xCD33 bispecific killer cell engager (BiKE) activates NK cells against primary MDS and MDSC CD33+ targets. Blood. 2014;123:3016-3026.
Schubert I, Kellner C, Stein C, et al. A single-chain triplebody with specificity for CD19 and CD33 mediates effective lysis of mixed lineage leukemia cells by dual targeting. MAbs. 2011;3:21-30.
Gleason MK, Verneris MR, Todhunter DA, et al. Bispecific and trispecific killer cell engagers directly activate human NK cells through CD16 signaling and induce cytotoxicity and cytokine production. Mol Cancer Ther. 2012;11:2674-2684.
Kügler M, Stein C, Kellner C, et al. A recombinant trispecific single-chain Fv derivative directed against CD123 and CD33 mediates effective elimination of acute myeloid leukaemia cells by dual targeting. Br J Haematol. 2010;150:574-586.
Braciak TA, Roskopf CC, Wildenhain S, et al. Dual-targeting triplebody 33-16-123 (SPM-2) mediates effective redirected lysis of primary blasts from patients with a broad range of AML subtypes in combination with natural killer cells. Oncoimmunology. 2018;7:e1472195.
Vallera DA, Felices M, Mcelmurry R, et al. 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;22:3440-3450.
Schmohl JU, Felices M, Oh F, et al. Engineering of anti-CD133 trispecific molecule capable of inducing NK expansion and driving antibody-dependent cell-mediated cytotoxicity. Cancer Res Treat. 2017;49:1140-1152.
Schmohl JU, Felices M, Taras E, Miller JS, Vallera DA. Enhanced ADCC and NK cell activation of an anticarcinoma bispecific antibody by genetic insertion of a modified IL-15 cross-linker. Mol Ther. 2016;24:1312-1322.
Schmohl JU, Felices M, Todhunter D, Taras E, Miller JS, Vallera DA. Tetraspecific scFv construct provides NK cell mediated ADCC and self-sustaining stimuli via insertion of IL-15 as a cross-linker. Oncotarget. 2016;7:73830-73844.
Zhou Q, Gil-Krzewska A, Peruzzi G, Borrego F. Matrix metalloproteinases inhibition promotes the polyfunctionality of human natural killer cells in therapeutic antibody-based anti-tumour immunotherapy. Clin Exp Immunol. 2013;173:131-139.
Romee R, Foley B, Lenvik T, et al. NK cell CD16 surface expression and function is regulated by a disintegrin and metalloprotease-17 (ADAM17). Blood. 2013;121:3599-3608.
Wiernik A, Foley B, Zhang B, et al. Targeting natural killer cells to acute myeloid leukemia in vitro with a CD16 x 33 bispecific killer cell engager and ADAM17 inhibition. Clin Cancer Res. 2013;19:3844-3855.
Chan WK, Kang S, Youssef Y, et al. A CS1-NKG2D bispecific antibody collectively activates cytolytic immune cells against multiple myeloma. Cancer Immunol Res. 2018;6:776-787.
Gauthier L, Morel A, Anceriz N, et al. Multifunctional natural killer cell engagers targeting NKp46 trigger protective tumor immunity. Cell. 2019;177:1701-1713.e16.e16.
Shimasaki N, Coustan-Smith E, Kamiya T, Campana D. Expanded and armed natural killer cells for cancer treatment. Cytotherapy. 2016;18:1422-1434.
Levy ER, Carlsten M, Childs RW. mRNA transfection to improve NK cell homing to tumors. Methods Mol Biol. 2016;1441:231-240.
Wu J. An activating immunoreceptor complex formed by NKG2D and DAP10. Science. 1999;285:730-732.
Bauer S. Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science. 1999;285:727-729.
Chang Y-H, Connolly J, Shimasaki N, Mimura K, Kono K, Campana D. A chimeric receptor with NKG2D specificity enhances natural killer cell activation and killing of tumor cells. Cancer Res. 2013;73:1777-1786.
Parihar R, Rivas C, Huynh M, et al. NK cells expressing a chimeric activating receptor eliminate MDSCs and rescue impaired CAR-T cell activity against solid tumors. Cancer Immunol Res. 2019;7:363-375.
Wang J, Lupo KB, Chambers AM, Matosevic S. Purinergic targeting enhances immunotherapy of CD73+ solid tumors with piggyBac-engineered chimeric antigen receptor natural killer cells. J Immunother Cancer. 2018;6:136.
Kamiya T, Seow SV, Wong D, Robinson M, Campana D. Blocking expression of inhibitory receptor NKG2A overcomes tumor resistance to NK cells. J Clin Invest. 2019;129:2094-2106.
Vitale M, Cantoni C, Pietra G, Mingari MC, Moretta L. Effect of tumor cells and tumor microenvironment on NK-cell function. Eur J Immunol. 2014;44:1582-1592.
Rouce RH, Shaim H, Sekine T, et al. The TGF-β/SMAD pathway is an important mechanism for NK cell immune evasion in childhood B-acute lymphoblastic leukemia. Leukemia. 2016;30:800-811.
Lee J-C, Lee K-Mi, Kim D-W, Heo DS. Elevated TGF-beta1 secretion and down-modulation of NKG2D underlies impaired NK cytotoxicity in cancer patients. J Immunol. 2004;172:7335-7340.
Meadows SK, Eriksson M, Barber A, Sentman CL. Human NK cell IFN-gamma production is regulated by endogenous TGF-beta. Int Immunopharmacol. 2006;6:1020-1028.
Lazarova M, Steinle A. Impairment of NKG2D-mediated tumor immunity by TGF-β. Front Immunol. 2019;10:2689.
Yang Bo, Liu H, Shi W, et al. Blocking transforming growth factor-β signaling pathway augments antitumor effect of adoptive NK-92 cell therapy. Int Immunopharmacol. 2013;17:198-204.
Yvon ES, Burga R, Powell A, et al. Cord blood natural killer cells expressing a dominant negative TGF-β receptor: implications for adoptive immunotherapy for glioblastoma. Cytotherapy. 2017;19:408-418.
Zhao Y, Hu Jinyue, Li Rongguo, et al. Enhanced NK cell adoptive antitumor effects against breast cancer in vitro via blockade of the transforming growth factor-β signaling pathway. Onco Targets Ther. 2015;8:1553-1559.
Konstantinidis KV, Alici E, Aints A, Christensson B, Ljunggren H-G, Dilber MS. Targeting IL-2 to the endoplasmic reticulum confines autocrine growth stimulation to NK-92 cells. Exp Hematol. 2005;33:159-164.
Nagashima S, Mailliard R, Kashii Y, et al. Stable transduction of the interleukin-2 gene into human natural killer cell lines and their phenotypic and functional characterization in vitro and in vivo. Blood. 1998;91:3850-3861.
Jiang W, Zhang J, Tian Z. Functional characterization of interleukin-15 gene transduction into the human natural killer cell line NKL. Cytotherapy. 2008;10:265-274.
Jiang W, Zhang C, Tian Z, Zhang J. hIL-15 gene-modified human natural killer cells (NKL-IL15) augments the anti-human hepatocellular carcinoma effect in vivo. Immunobiology. 2014;219:547-553.
Imamura M, Shook D, Kamiya T, et al. Autonomous growth and increased cytotoxicity of natural killer cells expressing membrane-bound interleukin-15. Blood. 2014;124:1081-1088.
Levy E, Reger R, Segerberg F, et al. Enhanced bone marrow homing of natural killer cells following mRNA transfection with gain-of-function variant CXCR4R334X. Front Immunol. 2019;10:1262.
Mehta RS, Rezvani K. Chimeric antigen receptor expressing natural killer cells for the immunotherapy of cancer. Front Immunol. 2018;9:283.
Glienke W, Esser R, Priesner C, et al. Advantages and applications of CAR-expressing natural killer cells. Front Pharmacol. 2015;6:21.
Olson JA, Leveson-Gower DB, Gill S, Baker J, Beilhack A, Negrin RS. NK cells mediate reduction of GVHD by inhibiting activated, alloreactive T cells while retaining GVT effects. Blood. 2010;115:4293-4301.
Sotillo E, Barrett DM, Black KL, et al. Convergence of acquired mutations and alternative splicing of CD19 enables resistance to CART-19 immunotherapy. Cancer Discov. 2015;5:1282-1295.
Klingemann H, Boissel L, Toneguzzo F. Natural killer cells for immunotherapy - advantages of the NK-92 cell line over blood NK cells. Front Immunol. 2016;7:91.
Suck G, Odendahl M, Nowakowska P, et al. NK-92: an ‘off-the-shelf therapeutic’ for adoptive natural killer cell-based cancer immunotherapy. Cancer Immunol Immunother. 2016;65:485-492.
Gong JH, Maki G, Klingemann HG. Characterization of a human cell line (NK-92) with phenotypical and functional characteristics of activated natural killer cells. Leukemia. 1994;8:652-658.
Tonn T, Schwabe D, Klingemann HG, et al. Treatment of patients with advanced cancer with the natural killer cell line NK-92. Cytotherapy. 2013;15:1563-1570.
Zhang C, Oberoi P, Oelsner S, et al. Chimeric antigen receptor-engineered NK-92 cells: an off-the-shelf cellular therapeutic for targeted elimination of cancer cells and induction of protective antitumor immunity. Front Immunol. 2017;8:533.
Schönfeld K, Sahm C, Zhang C, et al. Selective inhibition of tumor growth by clonal NK cells expressing an ErbB2/HER2-specific chimeric antigen receptor. Mol Ther. 2015;23:330-338.
Murakami T, Nakazawa T, Natsume A, et al. Novel human NK cell line carrying CAR targeting EGFRvIII induces antitumor effects in glioblastoma cells. Anticancer Res. 2018;38:5049-5056.
Kobayashi E, Kishi H, Ozawa T, et al. A chimeric antigen receptor for TRAIL-receptor 1 induces apoptosis in various types of tumor cells. Biochem Biophys Res Commun. 2014;453:798-803.
Vasu S, Berg M, Davidson-Moncada J, Tian X, Cullis H, Childs RW. A novel method to expand large numbers of CD56(+) natural killer cells from a minute fraction of selectively accessed cryopreserved cord blood for immunotherapy after transplantation. Cytotherapy. 2015;17:1582-1593.
Granzin M, Soltenborn S, Müller S, et al. Fully automated expansion and activation of clinical-grade natural killer cells for adoptive immunotherapy. Cytotherapy. 2015;17:621-632.
Lowe E, Truscott LC, De Oliveira SN. In vitro generation of human NK cells expressing chimeric antigen receptor through differentiation of gene-modified hematopoietic stem cells. Methods Mol Biol. 2016;1441:241-251.
Ni Z, Knorr DA, Bendzick L, Allred J, Kaufman DS. Expression of chimeric receptor CD4ζ by natural killer cells derived from human pluripotent stem cells improves in vitro activity but does not enhance suppression of HIV infection in vivo. Stem Cells. 2014;32:1021-1031.
Knorr DA, Ni Z, Hermanson D, et al. Clinical-scale derivation of natural killer cells from human pluripotent stem cells for cancer therapy. Stem Cells Transl Med. 2013;2:274-283.
Wilber A, Linehan JL, Tian X, et al. Efficient and stable transgene expression in human embryonic stem cells using transposon-mediated gene transfer. Stem Cells. 2007;25:2919-2927.
Shimasaki N, Fujisaki H, Cho D, et al. A clinically adaptable method to enhance the cytotoxicity of natural killer cells against B-cell malignancies. Cytotherapy. 2012;14:830-840.
Li L, Liu LN, Feller S, et al. Expression of chimeric antigen receptors in natural killer cells with a regulatory-compliant non-viral method. Cancer Gene Ther. 2010;17:147-154.
Kebriaei P, Singh H, Huls MH, et al. Phase I trials using Sleeping Beauty to generate CD19-specific CAR T cells. J Clin Invest. 2016;126:3363-3376.
Kebriaei P, Izsvák Z, Narayanavari SA, Singh H, Ivics Z. Gene therapy with the sleeping beauty transposon system. Trends Genet. 2017;33:852-870.
Saito S, Nakazawa Y, Sueki A, et al. Anti-leukemic potency of piggyBac-mediated CD19-specific T cells against refractory Philadelphia chromosome-positive acute lymphoblastic leukemia. Cytotherapy. 2014;16:1257-1269.
Nakazawa Y, Huye LE, Dotti G, et al. Optimization of the PiggyBac transposon system for the sustained genetic modification of human T lymphocytes. J Immunother. 2009;32:826-836.
Nakazawa Y, Matsuda K, Kurata T, et al. Anti-proliferative effects of T cells expressing a ligand-based chimeric antigen receptor against CD116 on CD34(+) cells of juvenile myelomonocytic leukemia. J Hematol Oncol. 2016;9:27.
Romanski A, Uherek C, Bug G, et al. CD19-CAR engineered NK-92 cells are sufficient to overcome NK cell resistance in B-cell malignancies. J Cell Mol Med. 2016;20:1287-1294.
Boissel L, Betancur M, Lu W, et al. Retargeting NK-92 cells by means of CD19- and CD20-specific chimeric antigen receptors compares favorably with antibody-dependent cellular cytotoxicity. Oncoimmunology. 2013;2:e26527.
Boissel L, Betancur M, Wels WS, Tuncer H, Klingemann H. Transfection with mRNA for CD19 specific chimeric antigen receptor restores NK cell mediated killing of CLL cells. Leuk Res. 2009;33:1255-1259.
Müller T, Uherek C, Maki G, et al. Expression of a CD20-specific chimeric antigen receptor enhances cytotoxic activity of NK cells and overcomes NK-resistance of lymphoma and leukemia cells. Cancer Immunol Immunother. 2008;57:411-423.
Jiang H, Zhang W, Shang P, et al. Transfection of chimeric anti-CD138 gene enhances natural killer cell activation and killing of multiple myeloma cells. Mol Oncol. 2014;8:297-310.
Chen KH, Wada M, Firor AE, et al. Novel anti-CD3 chimeric antigen receptor targeting of aggressive T cell malignancies. Oncotarget. 2016;7:56219-56232.
Chen KH, Wada M, Pinz KG, et al. Preclinical targeting of aggressive T-cell malignancies using anti-CD5 chimeric antigen receptor. Leukemia. 2017;31:2151-2160.
Esser R, Müller T, Stefes D, 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;16:569-581.
Zhang Ge, Liu R, Zhu X, et al. Retargeting NK-92 for anti-melanoma activity by a TCR-like single-domain antibody. Immunol Cell Biol. 2013;91:615-624.
Oelsner S, Friede ME, Zhang C, et al. Continuously expanding CAR NK-92 cells display selective cytotoxicity against B-cell leukemia and lymphoma. Cytotherapy. 2017;19:235-249.
Chu J, Deng Y, Benson DM, et al. CS1-specific chimeric antigen receptor (CAR)-engineered natural killer cells enhance in vitro and in vivo antitumor activity against human multiple myeloma. Leukemia. 2014;28:917-927.
Han J, Chu J, Keung Chan W, et al. CAR-engineered NK cells targeting wild-type EGFR and EGFRvIII enhance killing of glioblastoma and patient-derived glioblastoma stem cells. Sci Rep. 2015;5:11483.
Genßler S, Burger MC, Zhang C, et al. Dual targeting of glioblastoma with chimeric antigen receptor-engineered natural killer cells overcomes heterogeneity of target antigen expression and enhances antitumor activity and survival. Oncoimmunology. 2016;5:e1119354.
Schönfeld K, Sahm C, Zhang C, et al. Selective inhibition of tumor growth by clonal NK cells expressing an ErbB2/HER2-specific chimeric antigen receptor. Mol Ther. 2015;23:330-338.
Liu H, Yang Bo, Sun Tingting, et al. Specific growth inhibition of ErbB2-expressing human breast cancer cells by genetically modified NK-92 cells. Oncol Rep. 2015;33:95-102.
Sahm C, Schönfeld K, Wels WS. Expression of IL-15 in NK cells results in rapid enrichment and selective cytotoxicity of gene-modified effectors that carry a tumor-specific antigen receptor. Cancer Immunol Immunother. 2012;61:1451-1461.
Altvater B, Landmeier S, Pscherer S, et al. 2B4 (CD244) signaling by recombinant antigen-specific chimeric receptors costimulates natural killer cell activation to leukemia and neuroblastoma cells. Clin Cancer Res. 2009;15:4857-4866.
Imai C, Iwamoto S, Campana D. Genetic modification of primary natural killer cells overcomes inhibitory signals and induces specific killing of leukemic cells. Blood. 2005;106:376-383.
Hoyos V, Savoldo B, Quintarelli C, et al. Engineering CD19-specific T lymphocytes with interleukin-15 and a suicide gene to enhance their anti-lymphoma/leukemia effects and safety. Leukemia. 2010;24:1160-1170.
Liu E, Tong Y, Dotti G, et al. Cord blood NK cells engineered to express IL-15 and a CD19-targeted CAR show long-term persistence and potent antitumor activity. Leukemia. 2018;32:520-531.
Liu E, Marin D, Banerjee P, et al. Use of CAR-transduced natural killer cells in CD19-positive lymphoid tumors. N Engl J Med. 2020;382:545-553.