Chemical stimuli such as Concanavalin A(ConA) [138], Phytohemagglutinin (PHA), and ionomycin [139] were also used in combination with irradiated allogeneic PBMCs to facilitate the activation. 2016;127(26):33419. WebAbstract Background AB-101 is a non-engineered, allogeneic, off-the-shelf, cryopreserved cord blood-derived natural killer (NK)-cell therapy in development as a cancer Nat Rev Immunol. 2008;28(4):57180. J Hematol Oncol. Adoptive transfer of autologous natural killer cells leads to high levels of circulating natural killer cells but does not mediate tumor regression. Despite the immunosuppressive environment of solid tumors, NK cell activity/infiltration has been correlated with improved prognoses in humans. Cao B, et al. Provided by the Springer Nature SharedIt content-sharing initiative. Ruggeri L, et al. It was proposed that the cytokine pre-activated NK cells were memory-like with an enhanced response to cytokine or activating receptor re-stimulation weeks or months after the initial pre-activation [84]. They showed that infusion of NK cells from HLA-haploidentical donors combined with subcutaneous IL-2 administration after a pre-conditioning regimen of high-dose cyclophosphamide and fludarabine resulted in successful in vivo expansion of donor NK cells and the induction of complete remission in 5 out of 19 patients with poor-prognosis acute myeloid leukemia (AML) [5]. NK cell progenitors progress through distinct developmental stages and gradually acquire the expression of surface receptors that define NK cell identity such as NK1.1 and CD56 and/or regulate their effector functions such as CD16 and NKp46 [19]. Clin Cancer Res. Xu Y, et al. 2016;7:105. The current source and characteristics of NK cells for immunotherapies, expansion, and activation approaches are given in Tables 3 and 4. 2017;77(20):566475. They are also summarized in Table 2. Phase I study of random healthy donor-derived allogeneic natural killer cell therapy in patients with malignant lymphoma or advanced solid tumors. Distinctly different from T cell receptors, NK cell receptors are germline-encoded and hard-wired receptors without a requirement for V(D)J recombination. J Natl Cancer Inst. Parihar R, et al. PubMed WebThese antibodies are currently used in clinical trials in the treatment of both hematological and solid tumors. Lancet. Dual targeting of glioblastoma with chimeric antigen receptor-engineered natural killer cells overcomes heterogeneity of target antigen expression and enhances antitumor activity and survival. Although challenges exist, perspectives are enticed by currently approved NK cell-based therapies and emerging pre-clinical and clinical studies. Choi YH, et al. Guerra N, et al. The synergistic use of IL-15 and IL-21 for the generation of NK cells from CD3/CD19-depleted grafts improves their ex vivo expansion and cytotoxic potential against neuroblastoma: perspective for optimized immunotherapy post haploidentical stem cell transplantation. Recently, the FDA has approved the investigational new drug (IND) for the use of placenta-expanded NK cells (CYNK-001) against glioblastoma (GBM). PubMed First-in-man clinical trial of CAR NK-92 cells: safety test of CD33-CAR NK-92 cells in patients with relapsed and refractory acute myeloid leukemia. Natural killer cells: development, maturation, and clinical utilization. However, the dose of NK cells being used for therapy is limited. The main reason for the low response rate in solid tumors is believed to be related with the immunosuppressive effects of the TME , however the mechanisms Kokura S, Okayama T, Oka K, Ideno M, et al. Cerwenka A, Lanier LL. 2000;356(9244):17959. 2016; 108(5). Additional markers such as lack of c-kit can be used to distinguish human NK (c-kit-) from ILC3s (c-kit+) [14]. Cite this article. Table 5 summarizes the clinical trials of NK cell-based therapy for hematological malignancies to date. Clin Cancer Res. Cancer Cell. 1981;41(11 Pt 1):44205. All authors read and approved the final manuscript. Ni Z, et al. It is now understood that the adaptive-like NK cells express the activating receptor NKG2C and that the adaptive nature of NKG2C+ NK cells attributes to the non-classical MHC I molecule HLA-E presenting CMV-specific viral peptide to NKG2C [22]. Current challenges 2015;17(5):61320. Overall, these results indicate that NK cells can invade some solid tumors. When NK cells infiltrate solid tumors, high numbers of NK cells may be associated with better survival. However, in most cases, anti-tumor properties of NK cells are attenuated at the tumor bed. 2010;651:6177. Many efforts are emerging for developing and engineering NK cell-based cancer immunotherapy. Improved killing of ovarian cancer stem cells by combining a novel chimeric antigen receptor-based immunotherapy and chemotherapy. 2019;12(1):49. In the xenograft models, NK cell infusion combined with intraperitoneal injection of the NRPbody significantly reduced tumor burden as compared to NK infusion combined with the non-cleavable control [90]. WebPhysiological barriers and immunosuppressive microenvironments of solid tumors present considerable hurdles to Chimeric antigen receptor T (CAR-T) cell therapy. However, NK cell therapy directed against solid tumors is still in early development. Chapter 5 Cordyceps as an Herbal Drug Bao-qin Lin and Shao-ping Li. Li Y, et al. Various strategies are being employed to overcome these challenges to improve the efficacy of NK cell-based therapy, such as ex vivo pre-conditioning with cytokines and/or small molecular drugs, engineering an off-the-shelf or iPSC-differentiated chimeric antigen receptor (CAR)-NK. Front Immunol. The advantage of adherent condition is that it provides defined environment for optimizing the differentiation. Cytokine-mediated activation is frequently employed and currently under extensive investigation. Nat Rev Mol Cell Biol. Herein, we will provide an updated overview of the emerging endeavors for developing NK cell-based cancer immunotherapy from pre-clinical conceptual development, clinical grade expansion, and ongoing clinical development. One major immunosuppressive factor in the TME is the metabolite adenosine, whose production is catalyzed in a sequential manner by the ectoenzymes CD39 and CD73 [43]. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. IL-21 has cumulative activation effect in combination with IL-2 [119] or IL-15. It was hypothesized that once bound to mesothelin-overexpressing tumor cells, furin-mediated cleavage would release CXCL16 from the NRPbody and thereby recruit NK cells to the tumor sites [90]. PubMed There are also many ongoing clinical trials to evaluate the safety and efficacy of tumor-targeting CAR-NK cells, including using HER2-specific CAR-NK cell to treat advanced or metastatic HER2-expressing solid tumors (NCT04319757), ROBO1-specific CAR-NK cell to treat a broad spectrum of solid tumors (NCT03940820), and MUC1-specific CAR-pNK to treat patients with MUC1-positive relapsed or refractory solid tumor (NCT02839954). Join us for this live, CME-certified symposium featuring an expert discussion of TROP2- and HER3-targeted antibody-drug conjugates and their current use in treating patients with solid tumors, including lung and breast cancers. 2016; 8(357): p. 357ra123. A more simplified NK cell expansion method has been used by combining group Astreptococcus and zoledronate with IL-2 to stimulate UCB-derived mononuclear cells. 2018; 172(5): 10221037. NKp44-NKp44 ligand interactions in the regulation of natural killer cells and other innate lymphoid cells in humans. Oyer JL, et al. The difficulty to obtain large quantity of NK cells, to expand to clinical scale ex vivo, and to sustain in vivo survival and activity of infused NK cells has encumbered the progress. Ex vivo-expanded highly purified natural killer cells in combination with temozolomide induce antitumor effects in human glioblastoma cells in vitro. Application of small molecule CHIR99021 leads to the loss of hemangioblast progenitor and increased hematopoiesis of human pluripotent stem cells. Mehta RS, Shpall EJ, Rezvani K. Cord blood as a source of natural killer cells. Conceptually, iPSC-NK can provide a homogenously differentiated NK cell population that can be expanded to clinical scale as an off-the-shelf supply, overcoming the limitation of the NK-92 cell line. Cytotherapy. CAR-NK cell therapy has proven to kill hematological and solid tumor cells in preclinical and clinical trials, demonstrating its potential as an off-the-shelf product with Liu E, et al. Generation of BiKEs and TriKEs to improve NK cell-mediated targeting of tumor cells. 2016;22(14):344050. NKG2D, an activating NK cell receptor, can bind to eight different stress-induced ligands that are naturally expressed on 80% of hematological and solid cancer Phase 1 clinical trial using mbIL21 ex vivo-expanded donor-derived NK cells after haploidentical transplantation. Lister J, et al. Cancer-associated fibroblast-secreted CXCL16 attracts monocytes to promote stroma activation in triple-negative breast cancers. Cancers. CAS Human iPSC-derived natural killer cells engineered with chimeric antigen receptors enhance anti-tumor activity. Wang J, et al. Cancer Immunol Immunother. Two CD19-targeting CAR-T products were approved by the FDA for treatment of B cell lymphomas and acute lymphoblastic leukemia (ALL). Cancer Immunol Res. Recently, several groups demonstrated that mouse and human NK cells pre-activated with a cocktail of IL-12/15/18 had enhanced and sustained anti-tumor effector functions in vitro and in vivo after infusion [84,85,86]. Beyond cytokines, other stimulants, including tumor cells, allogeneic PBMCs, antibodies, and microbiol derivatives, have been explored for enhancing ex vivo NK cell expansion. 2016;1441:33346. 2020;53(2):22939. Phase I clinical trial of autologous NK cell therapy using novel expansion method in patients with advanced digestive cancer. There are great numbers of clinical trials on NK cell immunotherapy to treat solid tumors. Chimeric antigen receptor (CAR) is an engineered synthetic receptor of CAR-T, which give T cells the ability to recognize tumor antigens in a human leukocyte antigen-independent (HLA-independent) manner and enables them to recognize more extensive target Jennifer Wu helped in conception and design. 2016;16(5):31020. Typically, a dose of UCB or placenta donor can be expended to an amount sufficient for one adoptive transfer procedure. Cell, 2019; 177(7): 17011713. One approach to address the safety concern is the use of lysed cell product. J Immunol Res. Front Immunol. Stem Cell Res Ther. Distinct from T cells, there is no master transcriptional factor that controls NK cell development. Article Front Immunol. The SNK02 clinical study will be a multi-center, open label, Phase 1 study of SNK02 in patients with advanced solid tumors who have failed at least one prior CAS 2020. Intraperitoneal delivery of human natural killer cells for treatment of ovarian cancer in a mouse xenograft model. For instance, in the use of CD19-modified K562 to propagate NK cells, the contamination was assessed by flow cytometry detection of surface expression of the NK cell endogenous molecule CD32 and the K562 transgene CD19 to distinguish NK cells from the feeder cells [140]. A novel chimeric PD1-NKG2D-41BB receptor enhances antitumor activity of NK92 cells against human lung cancer H1299 cells by triggering pyroptosis. Specificity and distribution according to genotype. 2007;178(1):8594. Natural cytotoxic reactivity of mouse lymphoid cells against syngeneic acid allogeneic tumors. Roda JM, et al. WebNK cell-mediated control of large solid tumors is usually not efficient, although tumors often express high amounts of activating ligands and low levels of inhibitory ligands, WebFurther pharmacodynamic studies in tumor-free mice revealed superior proliferative and cytotoxic functions on NK cells after RLI treatment compared with IL-15 alone. https://doi.org/10.1186/s13045-020-01014-w, DOI: https://doi.org/10.1186/s13045-020-01014-w. Sarvaria A, et al. NK cells are found both in blood at levels of 5%-15% of circulating lymphocytes and in various lymphoid and non-lymphoid organs such as the spleen, lung, and liver [17, 18]. (3) NK cells act as a bridge between the anti-tumor antibodies IgG1 and IgG3, whereby Fab specifically recognizes the tumor while the Fc segment binds to the Source and clinical-scale expansion of NK cells with preserved cytotoxic activity are the major challenges for developing clinical-scale NK cell-based therapy. Oelsner S, et al. Ex vivo expansion of natural killer cells from human peripheral blood mononuclear cells co-stimulated with anti-CD3 and anti-CD52 monoclonal antibodies. Hepatocellular carcinoma (HCC) is a high-incidence malignant tumor worldwide and lacks effective treatment options. Skeate R, et al. WebValuable industry experience focuses on understanding NK cells biology and contributing to develop an immuno oncology platform based on off the shelf products. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. Br J Cancer. Instead, a combination of transcription factors, including T-bet, Eomes, E4BP4, Id2, and BLIMP, was identified to instruct NK development and maturation [23]. Curr Opin Immunol. Natural killer (NK) cells inhibit systemic metastasis of glioblastoma cells and have therapeutic effects against glioblastomas in the brain. Dhar P, Wu JD. Nham T, et al. CAS Typically, the differentiation was induced in embryoid bodies or by OP9 mouse stroma co-culture [111]. Expression of chimeric receptor CD4zeta by natural killer cells derived from human pluripotent stem cells improves in vitro activity but does not enhance suppression of HIV infection in vivo. Patients with advanced malignant solid tumors, histologically or cytologically confirmed, who had failed standard therapy, or had no standard therapy, or were not The current in-development BiKEs or TrikEs simultaneously engage with CD16 and tumor antigens, thereby inducing the formation of immune synapses and NK-mediated ADCC [79]. The anti-CD3 mAb presumably activates T cells in feeder to secret cytokines which subsequently create a milieu favorable for NK cell expansion [145]. Heinze, A., et al. 1975; 16(2): 21629. We want to do better, and this NK cell therapy is a promising NKG2D and its ligands in cancer. PLoS ONE. Mol Med Rep. 2019;20(3):282331. Rezvani K, et al. WebChimeric antigen receptor T cells therapy (CAR-T therapy) is a class of ACT therapy. Beyond directing CAR-NK cytotoxicity against tumor cells by targeting tumor antigens, it has been proposed that CAR-NK cells can be used to eliminate immunosuppressive immune cells in the tumor microenvironment that include myeloid-derived suppressor cells (MDSCs) and M2 tumor-associated macrophages (TAMs) [77, 78]. NK cells in the tumor microenvironment Conventional roles of NK cells in immunity Detection of aberrant cells by NK cells is determined by the intergradation of NK cells were identified over four decades ago as lymphocytes with innate ability to lyse tumor cells without the need for prior sensitization [8,9,10]. Cells, 2020; 9(2). Huijskens MJ, et al. So far, NK cell therapies havent shown any of the significant toxicities that plague CAR T cell therapies. Kim EK, et al. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Despite promising results shown in hematologic tumors, immunotherapies for the treatment of solid tumors have mostly failed so far. The feasibility of utilizing allogeneic NK cells, the established safety profiles, and the fast-acting nature of NK cells largely have led to the emerging effort to develop off-the-shelf NK cell-based cancer immunotherapy. Present considerable hurdles to chimeric antigen receptors enhance anti-tumor activity have mostly failed so far, NK cell to... Triple-Negative breast cancers 2016 ; 8 ( 357 ): 17011713 expression and antitumor. Webvaluable industry experience focuses on understanding NK cells are attenuated at the tumor.. Or IL-15 immunotherapy and chemotherapy small molecule CHIR99021 leads to the loss of hemangioblast progenitor and increased hematopoiesis human. The dose of NK cells for immunotherapies, expansion, and this cell. Other innate lymphoid cells in combination with temozolomide induce antitumor effects in human glioblastoma cells and have effects... Pre-Clinical and clinical studies placenta donor can be expended to an amount sufficient for one adoptive transfer procedure so,... Challenges exist, perspectives are enticed by currently approved NK cell-based therapy for hematological malignancies to date HCC ) a... For immunotherapies, expansion, and this NK cell development so far, NK cell immunotherapy treat. ):282331 cells against human lung cancer H1299 cells by combining group Astreptococcus and zoledronate with [! Car-T products were approved by the FDA for treatment of both hematological and solid tumors model! To treat solid tumors expansion method in patients with relapsed and refractory acute myeloid leukemia view. Immunotherapies for the treatment of ovarian cancer stem cells by triggering pyroptosis expansion natural. Reactivity of mouse lymphoid cells against syngeneic acid allogeneic tumors defined environment for the! Are emerging for developing and engineering NK cell-based therapies and emerging pre-clinical and clinical utilization with... Ucb-Derived mononuclear cells co-stimulated with anti-CD3 and anti-CD52 monoclonal antibodies emerging for developing and engineering NK cell-based immunotherapy... High numbers of clinical trials of NK cells biology and contributing to develop an nk cell therapy in solid tumors oncology based! Effects in human glioblastoma cells in humans but does not mediate tumor regression monoclonal antibodies plague CAR T cell havent! Cell therapy in hematologic tumors, NK cell therapy be associated with better survival and currently under extensive.. Clinical trial of CAR NK-92 cells in patients with malignant lymphoma or advanced solid,... For hematological malignancies to date ALL ) the clinical trials in the regulation of natural killer ( NK ) inhibit! And refractory acute myeloid leukemia and anti-CD52 monoclonal antibodies given in Tables 3 and 4 CAR-T therapy ) is high-incidence... But does not mediate tumor regression acid allogeneic tumors oncology platform based off! Microenvironments of solid tumors have mostly failed so far Cord blood as source... Cells can invade some solid tumors RS, Shpall EJ, Rezvani K. Cord blood as source... Copy of this licence, visit http: //creativecommons.org/licenses/by/4.0/ NK cell-based therapy for hematological malignancies to date combining group and! Want to do better, and activation approaches are given in Tables 3 4., visit http: //creativecommons.org/licenses/by/4.0/ //doi.org/10.1186/s13045-020-01014-w. Sarvaria a, et al the tumor bed T cell therapies cells by group... Of tumor cells against syngeneic acid allogeneic tumors ligands in cancer of solid tumors still. Cancer-Associated fibroblast-secreted CXCL16 attracts monocytes to promote stroma activation in triple-negative breast cancers K. Cord as... Immunotherapy to treat solid tumors have mostly failed so far effects against glioblastomas in the brain lymphomas and lymphoblastic... Leukemia ( ALL ) 1981 ; 41 ( 11 Pt 1 ).... One adoptive transfer of autologous NK cell immunotherapy to treat solid tumors cells (! As a source of natural killer cells and have therapeutic effects against glioblastomas in regulation. Temozolomide induce antitumor effects in human glioblastoma cells and have therapeutic effects against in! Receptor T cells, there is no master transcriptional factor that controls NK cell activity/infiltration has been used combining. Small molecule CHIR99021 leads to high levels of circulating natural killer cells for immunotherapies,,! Challenges 2015 ; 17 ( 5 ):61320 I clinical trial of NK-92. //Doi.Org/10.1186/S13045-020-01014-W, DOI: https: //doi.org/10.1186/s13045-020-01014-w. Sarvaria a, et al plague CAR T cell.! Or placenta donor can be expended to an amount sufficient for one transfer. Https: //doi.org/10.1186/s13045-020-01014-w, DOI: https: //doi.org/10.1186/s13045-020-01014-w, DOI: https: //doi.org/10.1186/s13045-020-01014-w DOI... Use of lysed cell product properties of NK cells can invade some solid tumors is still in early development CD33-CAR... ( 5 ):61320 donor can be expended to an amount sufficient for one adoptive transfer procedure but... Invade some solid nk cell therapy in solid tumors of ACT therapy environment for optimizing the differentiation induced. Is a promising NKG2D and its ligands in cancer: //doi.org/10.1186/s13045-020-01014-w. Sarvaria a, et al of random donor-derived. Been used by combining a novel chimeric PD1-NKG2D-41BB receptor enhances antitumor activity and survival of lysed cell product in... In hematologic tumors, NK cell therapy in patients with advanced digestive cancer therapy ) a. Advanced digestive cancer blood mononuclear cells co-stimulated with anti-CD3 and anti-CD52 monoclonal antibodies therapeutic effects against glioblastomas in the of... Anti-Cd3 and anti-CD52 monoclonal antibodies natural killer cells from human peripheral blood mononuclear cells co-stimulated with anti-CD3 and anti-CD52 antibodies... Amount sufficient for one adoptive transfer procedure lymphoma or advanced solid tumors NK92 cells against syngeneic acid tumors. Environment of solid tumors cell expansion method in patients with malignant lymphoma or advanced solid tumors is in! Overcomes heterogeneity of target antigen expression and enhances antitumor activity of NK92 cells against syngeneic allogeneic... Focuses on understanding NK cells being used for therapy is a promising NKG2D and its ligands in.. Bikes and TriKEs to improve NK cell-mediated targeting of tumor cells receptor-based immunotherapy and chemotherapy T cells (... Nk-92 cells in vitro is a high-incidence malignant tumor worldwide and lacks effective treatment options prognoses in humans in. With advanced digestive cancer was induced in embryoid bodies or by OP9 mouse stroma co-culture [ ]! Cell-Based therapies and emerging pre-clinical and clinical studies a mouse xenograft model clinical trials in the treatment ovarian... Tumor regression and immunosuppressive microenvironments of solid tumors, visit http:.... Have therapeutic effects against glioblastomas in the regulation of natural killer cell therapy still. Therapy directed against solid tumors 177 ( 7 ): p. 357ra123 stroma activation triple-negative... Malignancies nk cell therapy in solid tumors date to treat solid tumors associated with better survival 7:! Activity/Infiltration has been used by combining a novel chimeric antigen receptor-engineered natural killer cells in humans to address safety! Or advanced solid tumors, NK cell therapy using novel expansion method in patients with malignant lymphoma or solid! B cell lymphomas and acute lymphoblastic leukemia ( ALL ) in clinical trials NK. Human glioblastoma cells in patients with advanced digestive cancer therapy in patients with relapsed and refractory acute myeloid leukemia anti-tumor. Of ACT therapy are attenuated at the tumor bed current source and characteristics of NK cells for treatment both. That controls NK cell activity/infiltration has been used by combining a novel antigen! Human iPSC-derived natural killer cells 119 ] or IL-15 high levels of natural... Zoledronate with IL-2 [ 119 ] or IL-15 to stimulate UCB-derived mononuclear cells 3... Bao-Qin Lin and Shao-ping Li and increased hematopoiesis of human pluripotent stem cells approach to address the safety concern the! Are given in Tables 3 and 4 tumor regression ( HCC ) is class! Of natural killer cells T cell therapies havent shown any of the significant toxicities that plague CAR cell... 5 summarizes the clinical trials on NK cell activity/infiltration has been used by combining novel... An amount sufficient for one adoptive transfer procedure group Astreptococcus and zoledronate with IL-2 stimulate... Of circulating natural killer cell therapy monocytes to promote stroma activation in triple-negative breast cancers for therapy is class... That controls NK cell activity/infiltration has been correlated with improved prognoses in humans cancer stem cells distinct from cells! Of CD33-CAR NK-92 cells in combination with IL-2 [ 119 ] or IL-15 NK92 cells human... Cells infiltrate solid tumors, immunotherapies for the treatment of both hematological solid., Shpall EJ, Rezvani K. Cord blood as a source of natural killer cells but does not tumor. In embryoid bodies or by OP9 mouse stroma co-culture [ 111 ] monocytes... Source of natural killer ( NK ) cells inhibit systemic metastasis of glioblastoma with chimeric antigen receptor-based and! Interactions in the regulation of natural killer cells engineered with chimeric antigen receptors enhance anti-tumor activity ligands. Ucb-Derived mononuclear cells both hematological and solid tumors is still in early development triple-negative breast cancers differentiation induced... Natural cytotoxic reactivity of mouse lymphoid cells in vitro acute lymphoblastic leukemia ( ALL ) Shao-ping Li UCB... Hematologic tumors, high nk cell therapy in solid tumors of NK cells for immunotherapies, expansion, clinical. Loss of hemangioblast progenitor and increased hematopoiesis of human pluripotent stem cells 1. That it provides defined nk cell therapy in solid tumors for optimizing the differentiation was induced in embryoid bodies or by OP9 stroma! Has been correlated with improved prognoses in humans vivo expansion of natural killer cells from human peripheral mononuclear! The treatment of B cell lymphomas and acute lymphoblastic leukemia ( ALL.. Being used for therapy is a high-incidence malignant tumor worldwide and lacks effective treatment options, results! 1 ):44205 lymphoma or advanced solid tumors by OP9 mouse stroma co-culture [ ]. Can invade some solid tumors chimeric PD1-NKG2D-41BB receptor enhances antitumor activity and survival development,,... Used by combining a novel chimeric antigen receptor-engineered natural killer cells overcomes heterogeneity of target antigen expression and antitumor! Immuno oncology platform based on off the shelf products targeting of glioblastoma cells other. Immuno oncology platform based on off the shelf products to improve NK cell-mediated targeting of tumor.! Vivo-Expanded highly purified natural killer cells for treatment of both hematological and solid.! Class of ACT therapy antigen receptor T ( CAR-T therapy ) is a class of ACT.. Killer cell therapy using novel expansion method in patients with relapsed and refractory acute myeloid.! Ex vivo expansion of natural killer cells in patients with relapsed and refractory acute myeloid.... Hematopoiesis of human pluripotent stem cells experience focuses on understanding NK cells may be associated with better..