Prospect of Natural Killer Cells in Cancer Imunotherapy

Anna Meiliana, Nurrani Mustika Dewi, Andi Wijaya

Abstract


BACKGROUND: Current understanding in molecular character of natural killer (NK) cell, its function and mechanisms, send people the ideas to develop a NK cell-based immunotherapeutic strategies against human cancer.

CONTENT: Before being regards as a cell-based cellular therapy, NK cell have to be clinical proven. Early studies with NK cells infusions for acute myeloid leukemia and lung cancer showed a promising result. NK cells need simplified methods for enriching and expanding, in addition to its transfection with chimeric antigen receptors (CARs). NK-92 arise as an assuring effector cells to augment monoclonal and bispecific antibody therapy. Thus, NK cells show a potential opportunity for cell engineering, outstep the era of T cells.

SUMMARY: It is believed that NK cells bring a bright hope for future cancer immunotherapies, either alone or in combination as a harmonious therapy.

KEYWORDS: NK cells, NK-92 cells, immunotherapy, CAR


Full Text:

PDF

References


Brentjens RJ, Davila ML, Riviere I, Park J, Wang X, Cowell LG, et al. CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci Transl Med. 2013; 5: 177ra38, CrossRef.

Kalos M, Levine BL, Porter DL, Katz S, Grupp SA, Bagg A, et al. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med. 2011; 3: 95ra73, CrossRef.

Kochenderfer JN, Dudley ME, Feldman SA, Wilson WH, Spaner DE, Maric I, et al. B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-anti-gen-receptor-transduced T cells. Blood. 2012; 119: 2709-20, CrossRef.

Klingemann H, Boissal L, Toneguzzo F. Natural killer cells for immunotherapy – advantages of the NK-92 cell line over blood NK cells. Front Immunol. 2016; 7: 91, CrossRef.

Suck G, Odendahi M, Nowakowska P, Seidi C, Wels WS, Klingeman HG, et al. NK‐92: an ‘off‐the‐shelf therapeutic’ for adoptive natural killer cell‐based cancer immunotherapy. Cancer Immunol Immunother. 2015; 65: 485-92, CrossRef.

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: 239-52, CrossRef.

Iannello A, Thompson TW, Ardolino M, Marcus A, Raulet DH. Immunosurveillance and immunotherapy of tumors by innate immune cells. Curr Opin Immunol. 2016; 38: 52-8, CrossRef.

Koch J, Steinle A, Watzl C, Mandelboim O. Activating natural cytotoxicity receptors of natural killer cells in cancer and infection. Trends Immunol. 2013; 34: 182-91, CrossRef.

Shifrin N, Raulet DH, Ardolino M. NK cell self tolerance, responsiveness and missing self recognition. Semin Immunol. 2014; 26: 138-44, CrossRef.

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: 486-91, CrossRef.

Velardi A, Ruggeri L, Mancusi A, Aversa F, Christiansen FT. Natural killer cell allorecognition of missing self in allogeneic hematopoietic transplantation: a tool for immunotherapy of leukemia. Curr Opin Immunol. 2009; 21: 525-30, CrossRef.

Oelsner S, Friede M, Zhang C, Wagner J, Badura S, Bader P, et al. Continuously expanding CAR NK-92 cells display selective cytotoxicity against B-cell leukemia and lymphoma. Cytotherapy. 2017; 19: 235-49, CrossRef.

Tonn T, Becker S, Esser R, Schwabe D, Seifried E. Cellular immunotherapy of malignancies using the clonal natural killer cell line NK-92. J Hematother Stem Cell Res. 2001; 10: 535-44, CrossRef.

Arai S, Meagher R, Swearingen M, Myint H, Rich E, Martinson J, et al. Infusion of the allogeneic cell line NK-92 in patients with advanced renal cell cancer or melanoma: a phase I trial. Cytotherapy. 2008; 10: 625-32, CrossRef.

Tonn T, Schwabe D, Klingemann HG, Becker S, Esser R, Koehl U, et al. Treatment of patients with advanced cancer with the natural killer cell line NK-92. Cytotherapy. 2013; 15: 1563-70, CrossRef.

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: 376-83, CrossRef.

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: 1255-9, CrossRef.

Altvater B, Landmeier S, Pscherer S, Temme J, Schweer K, Kailayangiri 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: 4857-66, CrossRef.

Uherek C, Tonn T, Uherek B, Becker S, Schnierle B, Klingemann HG, et al. Retargeting of natural killer-cell cytolytic activity to ErbB2-expressing cancer cells results in efficient and selective tumor cell destruction. Blood. 2002; 100: 1265-73, PMID.

Schönfeld K, Sahm C, Zhang C, Naundorf S, Brendel C, Odendahl M, et al. Selective inhibition of tumor growth by clonal NK cells expressing an ErbB2/HER2-specific chimeric antigen receptor. Mol Ther. 2015; 23: 330-8, CrossRef.

Zhang C, Burger MC, Jennewein L, Genßler S, Schönfeld K, Zeiner P, et al. ErbB2/HER2-specific NK cells for targeted therapy of glioblastoma. J Natl Cancer Inst. 2016; 108: djv375, CrossRef.

Sutlu T, Nystrom 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: 1090-100, CrossRef.

Maki G, Klingemann HG, Martinson JA, Tam YK. Factors regulating the cytotoxic activity of the human natural killer cell line, NK-92. J Hematother Stem Cell Res. 2001; 10: 369-83, CrossRef.

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: 1451-61, CrossRef.

Müller T, Uherek C, Maki G, Chow KU, Schimpf A, Klingemann HG, 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: 411-23, CrossRef.

Esser R, Muller T, Stefes D, Kloess S, Seidel D, Gillies SD, et al. NK cells engineered to express a GD2 -specific antigen receptor display built-in ADCC-like activity against tumour cells of neuroectodermal origin. J Cell Mol Med. 2012; 16: 569-81, CrossRef.

Chu J, Deng Y, Benson DM, He S, Hughes T, Zhang J, 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: 917-27, CrossRef.

Han J, Chu J, Keung Chan W, Zhang J, Wang Y, Cohen JB, 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, CrossRef.

Vivier E, Raulet DH, Moretta A, Caligiuri MA, Zitgovel L, Lanier LL, et al. Innate or Adaptive Immunity? The Example of Natural Killer Cells. Science. 2011; 331: 44-9, CrossRef.

Trinchieri, G. Biology of natural killer cells. Adv Immunol. 1989; 47: 187-376, CrossRef.

Vivier E, Nunes JA, Vely F. Natural killer cell signaling pathways. Science. 2004; 306: 1517-9, CrossRef.

Lanier LL. NK cell recognition. Annu Rev Immunol. 2005; 23: 225-74, CrossRef.

Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S. Functions of natural killer cells. Nat Immunol. 2008; 9: 503-10, CrossRef.

Yokoyama WM, Plougastel BF. Immune functions encoded by the natural killer gene complex. Nat Rev Immunol. 2003; 3: 304-16, CrossRef.

Parham P. MHC class I molecules and KIRs in human history, health and survival. Nat Rev Immunol. 2005; 5: 201-14, CrossRef.

Kärre K, Ljunggren HG, Piontek G, Kiessling, R. Selective rejection of H- 2–deficient lymphoma variants suggests alternative immune defense strategy. Nature. 1986; 319: 675-8, CrossRef.

Raulet DH, Vance RE. Self-tolerance of natural killer cells. Nat Rev Immunol. 2006; 6: 520-31, CrossRef.

Karlhofer FM, Ribaudo RK, Yokoyama WM. MHC Class I Alloantigen Specificity of Ly-49+ IL-2-Activated Natural Killer Cells. Nature. 1992; 358: 66-70, article.

Moretta A, Bottino C, Vitale M, Pende D, Biassoni R, Mingari MC, et al. Receptors for HLA class-I molecules in human natural killer cells. Annu Rev Immunol. 1996; 14: 619-48, CrossRef.

Raulet DH, Guerra N. Oncogenic stress sensed by the immune system: role of natural killer cell receptors. Nat Rev Immunol. 2009; 9: 568-80, CrossRef.

Orange JS. Human natural killer cell deficiencies. Curr Opin Allergy Clin Immunol. 2006; 6: 399-409, CrossRef.

Berke G. The CTL's kiss of death. Cell. 1995; 81: 9-12, CrossRef.

Kim S, Iizuka K, Aguila HL, Weissman IL, Yokoyama WM. In vivo natural killer cell activities revealed by natural killer cell­deficient mice. Proc Natl Acad Sci USA. 2000; 97: 2731-6, CrossRef.

Mocikat R, Braumuller H, Gumy A, Egeter O, Ziegler H, Reusch U, et al. Natural killer cells activated by MHC class I(low) targets prime dendritic cells to induce protective CD8 T cell responses. Immunity. 2003; 19: 561-9, CrossRef.

Smyth MJ, Cretney E, Kelly JM, Westwood JA, Street SE, Yagita H, et al. Activation of NK cell cytotoxicity. Mol Immunol. 2005; 42: 501-10, CrossRef.

Tripp CS, Wolf SF, Unanue ER. Interleukin 12 and tumor necrosis factor alpha are costimulators of interferon gamma production by natural killer cells in severe combined immunodeficiency mice with listeriosis, and interleukin 10 is a physiologic antagonist. Proc Natl Acad Sci USA. 1993; 90: 3725-9, CrossRef.

Wallach D, Fellous M, Revel M. Preferential effect of gamma interferon on the synthesis of HLA antigens and their mRNAs in human cells. Nature. 1982; 299: 833-36, CrossRef.

Filipe­Santos O, Bustamante J, Chapgier A, Vogt G, de Beaucoudrey L, Feinberg J, et al. Inborn errors of IL­12/23­ and IFN­gamma­mediated immunity: molecular, cellular, and clinical features.. Semin Immunol. 2006; 18: 347-61, CrossRef.

Maher SG, Romero­Weaver AL, Scarzello AJ, Gamero AM. Interferon: cellular executioner or white knight? Curr Med Chem. 2007; 14: 1279-89, CrossRef.

Cooper MA, Fehniger TA, Turner SC, Chen KS, Ghaheri BA, Ghayur T, et al. Human natural killer cells: a unique innate immunoregulatory role for the CD56(bright) subset. Blood. 2001; 97: 3146-51, CrossRef.

Walzer T, Jaeger S, Chaix J, Vivier E. Natural killer cells: from CD3(­)NKp46(+) to post­genomics meta­analyses. Curr Opin Immunol. 2007; 19: 365-72, CrossRef.

Romagnani C, Juelke K, Falco M, Morandi B, D’Agostino A, Costa R, et al. CD56brightCD16­ killer Ig­like receptor­NK cells display longer telomeres and acquire features of CD56dim NK cells upon activation. J Immunol. 2007; 178: 4947-55, CrossRef.

Chan A, Hong DL, Atzberger A, Kollnberger S, Filer AD, Buckley CD, et al. CD56bright human NK cells differentiate into CD56dim cells: role of contact with peripheral fibroblasts. J Immunol. 2007; 179: 89-94, CrossRef.

Ouyang Q, Baerlocher G, Vulto I, Lansdorp PM. Telomere length in human natural killer cell subsets. Ann NY Acad Sci. 2007; 1106: 240-52, CrossRef.

Takahashi E, Kuranaga N, Satoh K, Habu Y, Shinomiya N, Asano T, et al. Induction of CD16+ CD56bright NK cells with antitumour cytotoxicity not only from CD16­ CD56bright NK cells but also from CD16­ CD56dim NK cells. Scand J Immunol. 2007; 65: 126-38, CrossRef.

Caliguiri MA. Human natural killer cells. Blood. 2008; 112: 461-9, CrossRef.

Klingemann HG. Cellular therapy of cancer with natural killer cells—where do we stand? Cytotherapy. 2013; 15: 1185-94, CrossRef.

Huntington ND, Vosshenrich CA, Di Santo JP. Developmental pathways that generate natural-killer-cell diversity in mice and humans. Nat Rev Immunol. 2007; 7: 703-14, CrossRef.

Guillerey C, Huntington ND, smyth MJ. Targeting natural killer cells in cancer immunotherapy. Nat Immunol. 2016; 17: 1025-36, CrossRef.

Voskoboinik I, Smyth MJ, Trapani JA. Perforin-mediated target-cell death and immune homeostasis. Nat Rev Immunol. 2006; 6: 940-52, CrossRef.

Sungur CM, Murphy WJ. Positive and negative regulation by NK cells in cancer. Crit Rev Oncog. 2014; 19: 57-66, CrossRef.

Iannello A, Thompson TW, Ardolino M, Lowe SW, Raulet DH. p53-dependent chemokine production by senescent tumor cells supports NKG2D-dependent tumor elimination by natural killer cells. J Exp Med. 2013; 210: 2057-69, CrossRef.

Becker PS, Suck G, Nowakowska P, Ullrich E, Seifried E, Bader P, et al. Selection and expansion of natural killer cells for NK cell-based immunotherapy. Cancer Immunol Immunother. 2016; 65: 477-84, CrossRef.

Knorr DA, Bachanova V, Verneris MR, Miller JS. Clinical utility of natural killer cells in cancer therapy and transplantation. Semin Immunol. 2014; 26: 161-72, CrossRef.

Parkhurst MR, Riley JR, Dudley ME, Rosenberg SA. Adoptively transferred autologous natural killer cells persist in circulation but do not mediate tumor regression. Clin Canc Res. 2011; 17: 6287-97, CrossRef.

Krause SW, Gastpar R, Andresen R, Gross C, Ullrich H, Thonigs G, et al. Treatment of colon cancer patients with ex vivo heat shock protein 70 peptide-activated, autologous natural killer cells: a clinical phase I trial. Clin Cancer Res. 2004; 10: 3699-707, CrossRef.

Motohashi S, Ishikawa A, Ishikawa E, Otsuji M, Iizasa T, Haoaka H, et al. A phase I study of ex vivo expanded natural killer T cells in patients with advanced and recurrent non-small lung cancer. Clin Cancer Res. 2006; 12: 6079-86, CrossRef.

Koepsell SA, Miller JS, McKenna DH Jr. Natural killer cells: a review of manufacturing and clinical utility. Transfusion. 2013; 53: 404-10, CrossRef.

McKenna DH Jr, Sumstad D, Bostrom N, Kadidlo DM, Fautsch S, McNearney S, et al. Good manufacturing practices production of natural killer cells for immunotherapy: a six year single-institution experience. Transfusion. 2007; 47: 520-8, CrossRef.

Boissel L, Tuncer HH, Betancur M, Wolfberg A, Klingemann H. Umbilical cord mesenchymal stem cells increase expansion of cord blood natural killer cells. Biol Blood Marrow Transplant. 2008; 14: 1031-8, CrossRef.

Lapteva N, Durett AG, Sun J, Rollins L, Dandekar V, Mei Z, et al. Large-scale ex vivo expansion and characterization of natural killer cells for clinical application. Cytotherapy. 2012; 14: 1131-43, CrossRef.

Ljunggren HG, Malmberg KJ. Prospects for the use of NK cells in immunotherapy of human cancer. Nat Rev Immunol. 2007; 7: 329-39, CrossRef.

Clausen J, Wolf D, Petzer AL, Gunsilius E, Schumacher P, Kircher B, et al. Impact of natural killer cell dose and donor killer-cell immunoglobulin-like receptor (KIR) genotype on outcome following human leucocyte antigen-identical haematopoietic stem cell transplantation. Clin Exp Immunol. 2007; 148: 520-8, CrossRef.

Tanaka M, Kobayashi S, Numata A, Tachibana T, Takasaki H, Maruta A, et al. The impact of the dose of natural killer cells in the graft on severe acute graft-versus-host disease after unrelated bone marrow transplantation. Leuk Res. 2012; 36: 699-703, CrossRef.

Locatelli F, Moretta F, Brescia L, Merli P. Natural killer cells in the treatment of high-risk acute leukaemia. Semin Immunol. 2014; 26: 173-9, CrossRef.

Domogala A, Madrigal J, Saudemont A. Natural killer cell immunotherapy: from bench to bedside. Front Immunol. 2015; 6: 264, CrossRef.

Xing D, Ramsay A, Gribben JG, Decker WK, Burks JK, Munsell M, et al. Cord blood natural killer cells exhibit impaired lytic immunological synapse formation that is reversed with IL-2 exvivo expansion. J Immunother. 2010; 33: 684-96, CrossRef.

Shah N, Martin-Antonio B, Yang H, Ku S, Lee DA, Cooper LJ, et al. Antigen presenting cell-mediated expansion of human umbilical cord blood yields log-scale expansion of natural killer cells with anti-myeloma activity. PLoS ONE. 2013; 8: e76781, CrossRef.

Blum KS, Pabst R. Lymphocyte numbers and subsets in the human blood. Do they mirror the situation in all organs? Immunol Lett. 2007; 108: 45-51, CrossRef.

Klingemann H, Grodman C, Cutler E, Duque M, Kadidlo D, Klein A, et al. Autologous stem cell transplant recipients tolerate haploidentical related-donor natural killer cell enriched infusions. Transfusion. 2013; 53: 412-8, CrossRef.

Klingemann H-G, Martinson J. Ex vivo expansion of natural killer cells for clinical application. Cytotherapy. 2004; 6: 15-22, CrossRef.

Yengar R, Handgretinger R, Babarin-Dorner A, Leimig T, Otto M, Geiger TL, et al. Purification of human natural killer cells using a clinical-scale immunomagnetic method. Cytotherapy. 2003; 5: 479-84, CrossRef.

Grzywacz B, Kataria N, Sikora M, Oostendorp RA, Dzierzak EA, Blazar BR, et al. Coordinated acquisition of inhibitory and activating receptors and functional properties by developing human natural killer cells. Blood. 2006; 108: 3824-33, CrossRef.

Domogala A, Madrigal J, Saudemont A. Cryopreservation has no effect on function of natural killer cells differentiated in vitro from umbilical cord blood CD34+ cells. Cytotherapy. 2016; 18: 754-9, CrossRef.

Luhm J, Brand JM, Koritke P, Hoppner M, Kirchner H, Frohn C. Large-scale generation of natural killer lymphocytes for clinical application. J Hematother Stem Cell Res. 2002; 11: 651-7, CrossRef.

Siegler U, Meyer-Monard S, Jorger S, Stern M, Tichelli A, Gratwohl A, et al. Good manufacturing practice-compliant cell sorting and large-scale expansion of single KIR-positive alloreactive human natural killer cells for multiple infusions to leukemia patients. Cytotherapy. 2010; 12: 750-63, CrossRef.

Meyer-Monard S, Passweg J, Siegler U, Kalberer C, Koehl U, Rovo A, et al. Clinical-grade purification of natural killer cells in haploidentical hematopoietic stem cell transplantation. Transfusion. 2009; 49: 362-71, CrossRef.

Fujisaki H, Kakuda H, Shimasaki N, Imai C, Ma J, Lockey T, et al. Expansion of highly cytotoxic human natural killer cells for cancer cell therapy. Cancer Res. 2009; 69: 4010-7, CrossRef.

Berg M, Lundqvist A, McCoy P Jr, Samsel L, Fan Y, Tawab A, et al. Clinical-grade ex vivo-expanded human natural killer cells up-regulate activating receptors and death receptor ligands and have enhanced cytolytic activity against tumor cells. Cytotherapy. 2009; 11: 341-55, CrossRef.

Lundqvist A, Yokoyama H, Smith A, Berg M, Childs R. Bortezomib treatment and regulatory T-cell depletion enhance the antitumor effects of adoptively infused NK cells. Blood. 2009; 113: 6120-7, CrossRef.

Miller JS, Soignier Y, Panoskaltsis-Mortari A, McNearney SA, Yun GH, Fautsch SK, et al. Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood. 2005; 105: 3051-7, CrossRef.

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: 652-8, PMID.

Tam YK, Martinson JA, Doligosa K, Klingemann HG. Ex vivo expansion of the highly cytotoxic human natural killer-92 cell-line under current good manufacturing practice condi- tions for clinical adoptive cellular immunotherapy. Cytotherapy. 2003; 5: 259-72, CrossRef.

Matsuo Y, Drexler HG. Immunoprofiling of cell lines derived from natural killer-cell and natural killer-like t-cell leukemia-lymphoma. Leuk Res. 2003; 27: 935-45, CrossRef.

NN. The key to unlocking CARs. Nat Biotechnol. 2017; 35: 889, CrossRef.

Bhat R, Watzl C. Serial killing of tumor cells by human natural killer cells--enhancement by therapeutic antibodies. PLoS One. 2007; 2: e326, CrossRef.

Klingemann H. Are natural killer cells superior CAR drivers. Oncoimmunol. 2014; 3: e28147, CrossRef.

Glienke W, Esser R, Priesner C, Suerth JD, Schambach A, Wels WS, et al. Advantages and applications of CAR-expressing natural killer cells. Front Pharmacol. 2015; 6: 21, CrossRef.

Daldrup-Link HE, Meier R, Rudelius M, Piontek G, Piert M, Metz S, et al. In vivo tracking of genetically engineered, anti-HER2/neu directed natural killer cells to HER2/neu positive mammary tumors with magnetic resonance imaging. Eur Radiol. 2005; 15: 4-13, CrossRef.

Romanski A, Uherek C, Bug G, Seifried E, Klingeman H, Wels WS, 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: 1287-94, CrossRef.

Velardi A. Natural killer cell alloreactivity 10 years later. Curr Opin Hematol. 2012; 19: 421-6, CrossRef.

Raffaghello L, Prigione I, Airoldi I, Camoriano M, Levreri I, Gambini C, et al. Downregulation and/or release of NKG2D ligands as immune evasion strategy of human neuroblastoma. Neoplasia. 2004; 6: 558-68, CrossRef.

Holdenrieder S, Eichhorn P, Beuers U, Samtleben W, Stieber P, Nagel D, et al. Soluble NKG2D ligands in hepatic autoimmune diseases and in benign diseases involved in marker metabolism. Anticancer Res. 2007; 27: 2041-5, PMID.

Kloess S, Huenecke S, Piechulek D, Esser R, Koch J, Brehm C, et al. IL-2-activated haploidentical NK cells restore NKG2D-mediated NK-cell cytotoxicity in neuroblastoma patients by scavenging of plasma MICA. Eur J Immunol. 2010; 40: 3255-67, CrossRef.

Sutlu T, Alici E. Natural killer cell-based immunotherapy in cancer: current insights and future prospects. J Intern Med. 2009; 266: 154-81, CrossRef.

Lee JH, Kim JS, Kim KH, Choi JE, Ji AY, Ting JT, et al. Comparison of cytotoxic dynamics between cytokine-induced killer cells and natural killer cells at the single cell level. J Immunol 2017; 198 (Supp 1): 198.12, article.

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: 955-9, CrossRef.

Miller JS. Therapeutic applications: natural killer cells in the clinic. Hematology Am Soc Hematol Educ Program. 2013; 2013: 247-53, CrossRef.




DOI: https://doi.org/10.18585/inabj.v10i3.532

Indexed by:

                 

                  

               

     

 

The Prodia Education and Research Institute