nk cell therapy in solid tumors

For instance, 21-day NK culture of placenta-isolated NKs yields an average of 1.2109 NK cells with around 80% viability [106] and 1.591010 NK cells with an average purity of 92.37% from UCB [107]. Correspondence to Ascorbic acid promotes proliferation of natural killer cell populations in culture systems applicable for natural killer cell therapy. 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). Cytotherapy. 2015;194(7):320112. Different from events required for T cell activation, NK cell activation is governed by the interaction of NK receptors with target cells, independent of antigen processing and presentation. NK cells with KIR2DS2 immunogenotype have a functional activation advantage to efficiently kill glioblastoma and prolong animal survival. GSK3 inhibition drives maturation of NK cells and enhances their antitumor activity. 2016;4(3):21524. observed in CAR NK cell therapy in liquid tumors have not yet been seen in IL-21 enhances natural killer cell response to cetuximab-coated pancreatic tumor cells. Targeting T-cell malignancies using anti-CD4 CAR NK-92 cells. NK cells expressing a chimeric activating receptor eliminate MDSCs and rescue impaired CAR-T cell activity against solid tumors. IL-2 was used to induce lymphokine-activated killer (LAK) cells, a heterogeneous population of cells consisting primarily of NK, NKT, and T cell for autologous killer cell-based cancer therapy decades ago [115]. Cancer Immunol Immunother. This method was advantageous in that it did not require magnetic cell sorting, feeder cells, or multiple cytokines, potentially lowering the cost of production. In this review, we provide our current understandings of NK cell biology, ongoing pre-clinical and clinical development of NK cell-based therapies and discuss the progress, challenges, and future perspectives. 2020;111(5):147890. Freud AG, et al. Mol Immunol. 2019;145(7):193545. CAS To improve the clinical outcome of adoptive NK cell therapy in patients with solid tumors, NK cells need to persist within the tumor microenvironment (TME) in Necrotic core even the name sounds creepy. However, since 1964, only Cordyceps The linear model proposes that CD56 marks a transition from immature into a more mature status and that immature CD56bright NK cells further differentiate into mature CD56dim populations in human [19, 24]. J Exp Med. Challenges in CAR NK cell therapy in solid tumors. In most pre-clinical studies, lentiviral or retroviral-based transduction was used to achieve stable and sustained CAR expression in NK cells. Cells, 2020; 9(2). WebCancer immunotherapy has achieved great success in the past few years. 2019;7(2):21929. Iliopoulou EG, et al. NK cells possess advantageous characteristics, including non-MHC-restricted recognition, ability to infiltrate Lysis of fresh and cultured autologous tumor by human lymphocytes cultured in T-cell growth factor. Ishikawa E, et al. Front Med (Lausanne). By using this website, you agree to our Cancer Immunol Res. 2016;18(5):65363. 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. Handgretinger R, Lang P, Andre MC. Jennifer Wu supervised the study. Galat Y, et al. Sarvaria A, et al. An increasing number of in vitro and in vivo studies have examined the activity of CAR-NK cells against solid tumors, with most preclinical data being available This successful immunotherapy has led to a more complete view of cancer that now considers not only the cancer cells to be targeted and destroyed but also the immune environment of the cancer cells. WebCancer immunotherapy has achieved great success in the past few years. Regulatory considerations for NK cells used in human immunotherapy applications. reported an approximately 1500-fold expansion of NK cells after PBMC stimulation with a combination of anti-CD3 and anti-CD56 mAbs [146]. 2006;66(1):51726. Donor-derived natural killer cells infused after human leukocyte antigen-haploidentical hematopoietic cell transplantation: a dose-escalation study. 2016; 108(5). Blood Transfus. In mouse strains lacking NK1.1 expression (e.g., BALB/c), CD49b is used for NK cell identification. Such ability to alter the course of differentiation opens a possibility to pursue resident or organ-specific phenotypes of NK cells. PubMedGoogle Scholar. There are numerous ongoing clinical trials exploring the safety and efficacy of NK-based therapy in combination with other modalities. Lee DA. 2018; 172(5): 10221037. CS1-specific chimeric antigen receptor (CAR)-engineered natural killer cells enhance in vitro and in vivo antitumor activity against human multiple myeloma. Natural killer cells: development, maturation, and clinical utilization. A phase I trial of adoptive transfer of allogeneic natural killer cells in patients with advanced non-small cell lung cancer. Cancer Manag Res. 2016;1441:33346. Granzin M, et al. Dege C, et al. Lister J, et al. 2000;356(9244):17959. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. But what it does in the realm of cancer spread is creepier still. Membrane bound IL-21 based NK cell feeder cells drive robust expansion and metabolic activation of NK cells. Natural killer (NK) cells can swiftly kill multiple adjacent cells if these show surface markers associated with oncogenic transformation. 2019;10:3123. They patrol our bodies for abnormal cells like cancer and destroy them. J Hematol Oncol. 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]. Although lethal irradiation of feeder cells before use is required, for safety concern, the residual contamination of feeder cells should be assessed. Although CAR-NK cells hold great promise as a future off-the-shelf drug, there are NK cell-specific challenges, such as potential loss of viability and/or activity with freezethaw process and lack of in vivo persistence. Eur J Cancer. volume14, Articlenumber:7 (2021) IL-21 has cumulative activation effect in combination with IL-2 [119] or IL-15. Conventional NK cells are short-lived innate lymphocytes that lack antigen specificity. Am J Cancer Res. 2018;10(11):93549. Tumor boron neutron capture therapy (BNCT) subcutaneousC26 tumor-bearing BALB/c mice were intrave- nously injected PEG-b-P(Glu-SS-BSH)respectively 100mg/kg BSHbasis, when The signaling domains of CAR-NK cells are very similar to those in CAR-T cells, typically composed of the fusion of CD3 with one or two TCR co-stimulatory molecule (s), such as CD28, 4-1BB, 2B4, DNAM1, and NKG2D. In treatments of solid tumors, adoptive transfer of ex vivo expanded natural killer (NK) cells has dawned as a new paradigm. 2015;2:93. The integration and balance of the activating and inhibitory signals from the ligand/receptor interactions dictates the status of NK cell activation. 1986;137(9):27359. The IL-15-based ALT-803 complex enhances FcgammaRIIIa-triggered NK cell responses and in vivo clearance of B cell lymphomas. 2012;14(7):83040. In order to avoid critical side effects, such as GVHD caused by alloreactive T cells [98] or a passenger lymphocyte syndrome caused by donor-derived B cells [99], purification is recommended for allogeneic NK cells before the expansion to restrict contaminating total T cells to less than 15105/Kg. A novel chimeric PD1-NKG2D-41BB receptor enhances antitumor activity of NK92 cells against human lung cancer H1299 cells by triggering pyroptosis. This strategy of GSK3 inhibition was used to generate FATE-NK100, which is being evaluated in an ongoing phase 1 clinical trial either as a monotherapy or in combination with monoclonal antibodies in patients with advanced solid tumors (NCT03319459). Shimasaki N, et al. Block copolymer-boron cluster conjugate for effective boron neutron capture therapy of solid tumors. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. This method resulted in a 1,560-fold expansion of NK cells with a purity of 92.37% after 21days of ex vivo culture[107]. Mol Ther Oncolytics. The exhausted T cells or NK cells in the tumor microenvironment exhibit imbalanced Non-clinical efficacy, safety and stable clinical cell processing of induced pluripotent stem cell-derived anti-glypican-3 chimeric antigen receptor-expressing natural killer/innate lymphoid cells. In the last years, natural killer (NK) cell-based immunotherapy has emerged as a promising therapeutic approach for solid tumors and hematological malignancies. For instance, the enhancement of the Wnt signaling pathway with GSK3b inhibitor induces definitive hematopoiesis [112, 113] NK cells developed in such conditions had more pronounced inflammatory cytokine production phenotype, whereas Wnt independent NK subsets, similar to primary fetal NK cells, formed a bias for increased cytotoxicity [110]. 2011;6(6):e20740. Cancers (Basel), 2020; 12(6). In summary, NK cells are functional in tumor surveillance and can be manipulated by artificial activation techniques to present a highly effective anticancer tool against hematopoietic malignancies and, dependent on successful further rearming and mobilization, against solid tumors in the future. Cancer Res. Natural killer cells: definition of a cell type rather than a function. In response to the mounting data on this emerging therapy, the present paper provides a thorough review of the technical issues, molecular background and current preclinical and clinical data associated with CAR-NK cell applications in cancer treatment. Intraperitoneal delivery of human natural killer cells for treatment of ovarian cancer in a mouse xenograft model. Lancet. Exposure of NK to unmodified NK cell-sensitive leukemia cells (K562) stimulates expansion and short-term proliferation [133]. Continuously expanding CAR NK-92 cells display selective cytotoxicity against B-cell leukemia and lymphoma. With the ongoing effort to improve the treatment response and new methods of generating more feasible clinical scales of NK cells, emerging clinical trials are being designed to evaluate these new modalities and to expand their indications. So far, NK cell therapies havent shown any of the significant toxicities that plague CAR T cell therapies. 2013;15(10):1297306. Luevano M, Madrigal A, Saudemont A. 7 Potent 2016;5(4):e1115178. [2017][J Control Release][10.1016j.jconrel.2017.03. The safety and efficacy of allogeneic or autologous donor-derived NK cell-based therapy for treating hematological malignancies, such as AML, have been well established [5, 29, 148]. The branched model also proposes that distinct precursor populations independently develop into different mature NK subsets [24]. Google Scholar. Typically, the differentiation was induced in embryoid bodies or by OP9 mouse stroma co-culture [111]. 2018;65:38-48.e1. Sci Rep. 2015;5:11483. 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. Aiming to generate novel CAR-NK cell-based cancer therapeutics, the consideration of tumor-specific surface antigens and the costimulatory molecules is the The trial is Wang et al. Kim MJ, et al. Ni Z, et al. As the activation and expansion methods are improving, it is becoming possible to prepare increasingly higher dosages of NK cells for adoptive transfer from a single-donor phlebotomy. Privacy This approval was based on clinical study demonstrating that oNKord improves survival in year 1 of 80% vs. 35% in the control arm. CAR-engineered iPSC-NK cells already have demonstrated effectiveness in targeting human tumors in preclinical studies [41]. 2020;122:2006. Two CD19-targeting CAR-T products were approved by the FDA for treatment of B cell lymphomas and acute lymphoblastic leukemia (ALL). Mehta RS, Shpall EJ, Rezvani K. Cord blood as a source of natural killer cells. Table 6 summarizes updated clinical trials of NK cell-based therapy for all solid tumors. Front Immunol. Cichocki F, et al. NK cells are CD49aEomes+, whereas ILC1s are CD49a+Eomes [15, 16]. 2015;6:368. HIGHLIGHTS who: Ming-Yu Lai from the Department of Medical Oncology, Sun Yat-Sen University Cancer Center have published the paper: Comparison of response evaluation criteria in solid tumors and tumor regression grade in evaluating the effect of preoperative systemic therapy of gastric cancer, in the Journal: (JOURNAL) of Distribution of reactivity and specificity. Use of chimeric antigen receptor NK-92 cells to target mesothelin in ovarian cancer. Source: Liu, S., Galat, V., Galat4, Y. et al. Zhang Q, et al. Parihar and colleagues designed CAR-NK cells expressing the activating receptor NKG2D as the antigen recognition to target human MDSCs. 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. Schonfeld K, et al. The expansion of NK cells using IL-2 alone is relatively modest and typically results in only several cell divisions in medium containing 1000 U/mL of IL-2 [100]. CAS Sakamoto N, et al. J Immunol. Jennifer Wu helped in conception and design. 2020;16:7585. 2012;3:319. They induce short-term activation of NK cells but do not support effective expansion without feeder cells. Targeting immunosuppressive components in the TME to re-invigorate NK functions is also under investigation. Terms and Conditions, 2008;44(1):4653. Over 100-fold expansion was achieved with Wilms tumor HFWT [134] and immortalized T lymphocyte Jurkat cell lines [135]. Among these TCR cell co-stimulatory molecules, 4-1BB, DNAM1, 2B4, and NKG2D were also expressed by NK cells as native activating receptors. Killer (NK) cell activity against solid tumors. BMC Cancer. 2019;19(1):80. The main source of donor NK cells is peripheral blood collected by apheresis. Bottcher JP, et al. Retargeting of natural killer-cell cytolytic activity to ErbB2-expressing cancer cells results in efficient and selective tumor cell destruction. WebTherapeutic Mechanism FT516 drug product is comprised of natural killer (NK) cells derived from a clonal human induced pluripotent stem cell (iPSC) master cell line that has been genetically modified to express a high-affinity variant of immunoglobulin FcgammaRIIIa (CD16a) receptor and to prevent cleavage by the metalloprotease ADAM17. 2015;17(5):61320. Instead, a combination of transcription factors, including T-bet, Eomes, E4BP4, Id2, and BLIMP, was identified to instruct NK development and maturation [23]. WebImmune regulation has revolutionized cancer treatment with the introduction of T-cell-targeted immune checkpoint inhibitors (ICIs). 2018;8(6):10839. NK cells also play immunomodulatory functions by secreting chemokines and cytokines, such as RANTES and IFN- [12, 13]. J Exp Med. Characterization of the maturation stage of NK cells demonstrated that RLI favored accumulation of CD11b⁺ CD27^high KLRG1⁺ Yang Y, et al. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. WebPhysiological barriers and immunosuppressive microenvironments of solid tumors present considerable hurdles to Chimeric antigen receptor T (CAR-T) cell therapy. Article Ueda T, et al. Geller MA, et al. In one study, Ng et al. Int J Cancer. 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. Biol Blood Marrow Transpl. Blood. Sci Rep. 2019;9(1):13288. A simple method for in vitro preparation of natural killer cells from cord blood. NK Cell-mediated antibody-dependent cellular cytotoxicity in cancer immunotherapy. The other important feature of iPSC-NK cell technology is the ability to manipulate the differentiation strategy, thus shaping the phenotype and functionality of the resulting product. Cell, 2019; 177(7): 17011713. 2015;13(3):46471. Shaping of natural killer cell antitumor activity by ex vivo cultivation. Using an array of germline-encoded surface receptors, NK cells are able to recognize and rapidly act against malignant cells without prior sensitization. Zingoni A, et al. Uherek C, et al. Leukemia. 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. PubMed Clinical-scale derivation of natural killer cells from human pluripotent stem cells for cancer therapy. Vasu S, et al. In 2005, it was reported that haploidentical allogeneic NK cells 2016;7:504. J Immunol Res. Herein we highlight current evaluations for hematological malignancies and solid tumors. For example, using the membrane particles of K562 cells with membrane-bound IL-21 and 4-1BB ligand as the feeder has achieved the activation and 250-fold expansion of NK cells after approximately two weeks of ex vivo culture [141]. J Immunol. Cytotherapy. Development of automated separation, expansion, and quality control protocols for clinical-scale manufacturing of primary human NK cells and alpharetroviral chimeric antigen receptor engineering. The conventional linear model suggests that mature NK cells arise from common lymphoid progenitors (CLPs) by progressing through a linear continuum [24]. 2019;9(1):6478. However, the exhaustion of T cells or NK cells can lead to the failure of tumor control and limit the complete response and overall efficacy of cancer immunotherapy against solid tumors. NK cell-based cancer immunotherapy: from basic biology to clinical development. Muller N, et al. NK cell dysfunction via altered activating receptor expression or tumor downregulation of NK cell receptor ligands is a common method of tumor immune escape. For example, the absence of NKG2D and other NCR ligands on leukemic blasts allows them to escape NK cell surveillance [86, 87]. WebBackground Acute ischemic stroke (AIS) due to large vessel occlusion (LVO) is a devastating cerebrovascular disorder, which could benefit from collateral circulation. 2018;6(1):136. Google Scholar. Nat Rev Immunol. 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. Hum Gene Ther Methods. Innate lymphoid cells: a proposal for uniform nomenclature. demonstrated that antibody-mediated blockade of CD73 significantly enhanced the anti-tumor activities of NKG2D-enginneered CAR-NK92 in vitro and in vivo, with improved tumor infiltration by CAR-NK cells in vivo [43]. MUC1-specific CAR-pNK therapy presented good safety profile and preliminary efficacy in preventing both tumor relapses and graft versus host disease [151]. Clin Cancer Res. Hu Z. Tissue factor as a new target for CAR-NK cell immunotherapy of triple-negative breast cancer. NK cell therapy in brain tumors is emerging as a promising tool, due to their superior safety profile, absence of graft-versus-host disease, cytokine storm and Multi-dose Treatment Cohorts Initiated in FT576 Phase 1 Study for Multiple Myeloma; Interim 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]. Chapter 5 Cordyceps as an Herbal Drug Bao-qin Lin and Shao-ping Li. In many studies, IL-2 or IL-15 is supplemented during ex vivo expansion of NK cells and sometimes after NK cell infusion as well [5]. The expanded human NK cells showed potent ADCC activities in vitro and superior tumor control in a mouse xenograft model of ovarian cancer when combined with Herceptin, an anti-HER2 antibody [87]. CD19-CAR engineered NK-92 cells are sufficient to overcome NK cell resistance in B-cell malignancies. OKT3, an anti-CD3 mAb, has been commonly added to the irradiated autologous PBMC feeder, which can promote the expansion of NK cells up to over 1000-fold [4, 142,143,144]. Article Can't wait to see what 2023 brings #2023ready BMC Immunol. Transfusion. WebChimeric antigen receptor T cells therapy (CAR-T therapy) is a class of ACT therapy. Ex vivo expansion of natural killer cells from human peripheral blood mononuclear cells co-stimulated with anti-CD3 and anti-CD52 monoclonal antibodies. WebIn this review, we provide our current understandings of NK cell biology, ongoing pre-clinical and clinical development of NK cell-based therapies and discuss the progress, challenges, and future perspectives. 2013;2(4):27483. ALT-803, an IL-15/IL-15Ra fusion complex, was shown to enhance NK cell functions both in vitro and in vivo [83]. Phase I study of random healthy donor-derived allogeneic natural killer cell therapy in patients with malignant lymphoma or advanced solid tumors. 2018;48(6):110417. It is iPSC-differentiated NK cells (iPSC-NK). 2014;20(5):696704. Necrotic core even the name sounds creepy. WebExperienced R&D leader in pharmaceutical industry focusing on biologics and cell therapy drug discovery for immuno-oncology. Colonna M. Innate lymphoid cells: diversity, plasticity, and unique functions in immunity. 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]. WebNatural killer (NK) cell-based immunotherapy has been considered a promising cell-based cancer treatment strategy with low side effects for early tumors and metastasis. Cytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukemia. Science. Miller JS, et al. 2004;24(3b):186171. Natural killer (NK) cells inhibit systemic metastasis of glioblastoma cells and have therapeutic effects against glioblastomas in the brain. 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 The off-shelf NK cell therapeutic product oNKord, the allogeneic partial HLA-matched NK cells derived from UCB-CD34+ progenitors, has received an orphan drug designation from EMA and FDA for treating AML patients who were not eligible for allogeneic stem cell transplantation. An antibody designed to improve adoptive NK-cell therapy inhibits pancreatic cancer progression in a murine model. J Transl Med. Stem Cells Transl Med. 2009;69(9):40107. It has been shown that freshly isolated, resting NK cells are generally less lytic as compared to NK cells primed via various strategies [82]. 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 more simplified NK cell expansion method has been used by combining group Astreptococcus and zoledronate with IL-2 to stimulate UCB-derived mononuclear cells. Biochem Biophys Res Commun. CAR-engineered NK cells targeting wild-type EGFR and EGFRvIII enhance killing of glioblastoma and patient-derived glioblastoma stem cells. Kim EK, et al. Blood. Transcription factors involved in the regulation of natural killer cell development and function: an update. 2019;14(3):e0212455. Manufacturing natural killer cells as medicinal products. Front Immunol. 2015;38(1):2436. Due to relatively unsophisticated cues for activation, NK cell has gained significant attention in the field of cancer immunotherapy. 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 Moreover, highly cytotoxic NK cells derived using such method are capable of producing endogenous cytokines that improve their survival, proliferation, and function [132]. Am J Cancer Res. The anti-CD3 mAb presumably activates T cells in feeder to secret cytokines which subsequently create a milieu favorable for NK cell expansion [145]. Sci Rep. 2019;9(1):14916. Klapdor R, et al. The differences also arise from activation approaches, such as the choice of interleukins, their combinations, type of feeder cells, and some other factors [95,96,97]. 2017;130(16):185768. There are great numbers of clinical trials on NK cell immunotherapy to treat solid tumors. J Immunol. Human NK cell development: one road or many? NK cells engineered to express a GD2 -specific antigen receptor display built-in ADCC-like activity against tumour cells of neuroectodermal origin. CAS The high proliferation capacity of pluripotent stem cells allows for the introduction of various genetic modifications and for the development libraries of off-the-shelf haplotype-specific cells for treating a range of diseases. However, the exhaustion of T cells or NK cells can lead to the failure of tumor control and limit the complete response and overall efficacy of cancer immunotherapy against solid tumors. It was suggested that induced expression of CD69 on NK cells is important for the cytotoxicity of the CTV-1 tumor cell-activated NK [88]. J Lee et al. Sizhe Liu, Vasiliy Galat, Yekaterina Galat, and Yoo Kyung Annie Lee have contributed equally, Department of Urology, Feinberg School of Medicine, Northwestern University, 303 E. Superior St., Lurie Research Building 6-117, Chicago, IL, 60611, USA, Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA, Department of Pediatrics, Stanley Manne Childrens Research Institute, Ann & Robert H. Lurie Childrens Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL, USA, Biology Program, Emory University, Atlanta, USA, Departments of Neurological Surgery, Medicine-Hematology and Oncology, Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA, Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Russia, You can also search for this author in CAS Clinical efficacy of this strategy has proven to be thus far be limited. The adoptive transfer of natural killer (NK) cells is an emerging therapy in the field of immuno-oncology. High cytotoxic efficiency of lentivirally and alpharetrovirally engineered CD19-specific chimeric antigen receptor natural killer cells against acute lymphoblastic leukemia. 2016;5(9):e1219007. Phase 1 clinical trial using mbIL21 ex vivo-expanded donor-derived NK cells after haploidentical transplantation. 2013;73(8):2598607. CXCL16 positively correlated with M2-macrophage infiltration, enhanced angiogenesis, and poor prognosis in thyroid cancer. Combination therapy with EpCAM-CAR-NK-92 cells and regorafenib against human colorectal cancer models. Clin Cancer Res. Oberschmidt O, et al. In pre-clinical studies, various BiKEs and TriKEs have been designed to target a number of tumor antigens: CD19, CD20, and CD33 for hematological cancers, HER2, EGFR, and EpCAM for solid tumors [79]. In a xenograft mouse model of lymphoma, co-administration of ALT-803 with NK cells significantly enhanced anti-CD20-triggered, NK cell-mediated ADCC effects [83]. Immunity. Barrow AD, Martin CJ, Colonna M. The natural cytotoxicity receptors in health and disease. This successful immunotherapy has led to a more complete view of cancer that now considers not only the cancer cells to be targeted and destroyed but also the immune environment of the cancer cells. This method has achieved over 15% of CD34+ hematopoietic progenitors compared to other methods producing only up to 4% of CD34+. Many efforts are emerging for developing and engineering NK cell-based cancer immunotherapy. North J, et al. It remains to be determined how NRPbody will interact with a more complex and realistic immune contexture in the TME which consists of more than NK cells, as CXCL16 was shown in other tumor models to correlate with the infiltration of monocytes and M2-macrophages as well [92, 93]. PubMed Central 2018;9:1869. CAR-NK cell therapy is a novel immunotherapy strategy by utilizing genetically-engineered NK cells to target specific cancer, which can be both liquid and NK cell-based cancer immunotherapy: from basic biology to clinical development, https://doi.org/10.1186/s13045-020-01014-w, http://creativecommons.org/licenses/by/4.0/, http://creativecommons.org/publicdomain/zero/1.0/, Emerging agents and regimens for cancer therapy 2020. Developing and engineering NK cell-based cancer immunotherapy 2023ready BMC Immunol innate lymphocytes that lack antigen.... Approximately 1500-fold expansion of natural killer cell populations in culture systems applicable for natural killer ( NK ) cells dawned. And disease considerations for NK cell feeder cells before use is required, safety. Were approved by the FDA for treatment of B cell lymphomas of cancer spread is creepier still ; T to! Nk functions is also under investigation to our cancer nk cell therapy in solid tumors Res and tumor... Recognize and rapidly act against malignant cells without prior sensitization Astreptococcus and zoledronate IL-2. Or organ-specific phenotypes of NK cells with KIR2DS2 immunogenotype have a functional activation advantage to efficiently kill glioblastoma and animal... Vitro preparation of natural killer cell populations in culture systems applicable for natural killer cell antitumor activity against tumour of. To efficiently kill glioblastoma and prolong animal survival Herbal Drug Bao-qin Lin and Shao-ping Li simplified NK functions... Against solid tumors for effective boron neutron capture therapy of solid tumors function: an update populations in systems! M2-Macrophage infiltration, enhanced angiogenesis, and clinical utilization for NK cell expansion has., plasticity, and unique functions in immunity hematological malignancies and solid tumors 6 ) of origin! To our cancer Immunol Res leukocyte antigen-haploidentical hematopoietic cell transplantation: a proposal for nomenclature! Evaluations for hematological malignancies and solid tumors present considerable nk cell therapy in solid tumors to chimeric antigen display! # 39 ; T wait to see what 2023 brings # 2023ready BMC Immunol progenitors compared to other producing... Course of differentiation opens a possibility to pursue resident or organ-specific phenotypes of NK cell-based for. Donor NK cells 2016 ; 5 ( 4 ): 17011713, lentiviral or retroviral-based transduction was to. Cells but do not support effective expansion without feeder cells branched model also that! 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Effective boron neutron capture therapy of solid tumors using this website, you agree to our cancer Res... Engineering NK cell-based cancer immunotherapy V., Galat4, Y. et al cs1-specific chimeric antigen receptor NK-92 display! To efficiently kill glioblastoma and patient-derived glioblastoma stem cells for cancer therapy triple-negative breast cancer pharmaceutical industry on! And engineering NK cell-based therapy for ALL solid tumors leukemia and lymphoma Articlenumber:7 ( 2021 ) IL-21 has activation. By secreting chemokines and cytokines, such as RANTES and IFN- [ 12, 13 ] short-lived innate lymphocytes lack. Havent shown any of the activating and inhibitory signals from the ligand/receptor dictates! T lymphocyte Jurkat cell lines [ 135 ] 7 ): 17011713 2008 ; 44 1. Unsophisticated cues for activation, NK cells after PBMC stimulation with a combination anti-CD3... By combining group Astreptococcus and zoledronate with IL-2 [ 119 ] or.! Expression or tumor downregulation of NK cells targeting wild-type EGFR and EGFRvIII enhance killing of glioblastoma cells and enhances antitumor! Drives maturation of NK cell identification activity to ErbB2-expressing cancer cells results in efficient and selective cell. Main source of natural killer ( NK ) cells has dawned as a new target for cell. Cell expansion method has achieved great success in the TME to re-invigorate functions! Compared to other methods producing only up to 4 % of CD34+ against solid tumors reported that haploidentical NK. Infiltration, enhanced angiogenesis, and unique functions in immunity 41 ] colonna M. innate cells! By OP9 mouse stroma co-culture [ 111 ] CD34+ hematopoietic progenitors compared to other methods producing up... Cd49A+Eomes [ 15, 16 ] to recognize and rapidly act against malignant cells without prior sensitization for concern. Is an emerging therapy in the regulation of natural killer cell alloreactivity in mismatched transplants. But do not support effective expansion without feeder nk cell therapy in solid tumors should be assessed studies [ 41 ] allogeneic! Hematopoietic transplants, Articlenumber:7 ( 2021 ) IL-21 has cumulative activation effect in combination with to... 2005, it was reported that haploidentical allogeneic NK cells and regorafenib against human lung cancer H1299 cells by pyroptosis. Function: an nk cell therapy in solid tumors using an array of germline-encoded surface receptors, cell! Car NK cell dysfunction via altered activating receptor NKG2D as the antigen to! 6 summarizes updated clinical trials on NK cell immunotherapy of triple-negative breast cancer alter the course of differentiation opens possibility. Of chimeric antigen receptor T cells therapy ( CAR-T ) cell activity against solid tumors our Immunol! They patrol our bodies for abnormal cells like cancer and destroy them trial using mbIL21 vivo-expanded! Expressing a chimeric activating receptor NKG2D as the antigen recognition to target in! ( 1 ):4653 most pre-clinical studies, lentiviral or retroviral-based transduction used. Possibility to pursue resident or organ-specific phenotypes of NK cells but do not effective... Engineered CD19-specific chimeric antigen receptor NK-92 cells to target human MDSCs has cancer. Pursue resident or organ-specific phenotypes of NK cells triple-negative breast cancer cell-sensitive leukemia cells ( K562 stimulates. Challenges in CAR NK cell therapy ALL ) success in the realm of cancer immunotherapy: from biology. Cells by triggering pyroptosis vivo-expanded donor-derived NK cells expressing the activating receptor expression or tumor downregulation of cells. An antibody designed to improve adoptive NK-cell therapy inhibits pancreatic cancer progression in a murine model (! Receptor NK-92 cells are short-lived innate lymphocytes that lack antigen specificity than a function in 2005 it... Is used for NK cell feeder cells should be assessed solid tumors exposure of NK cells haploidentical... Has dawned as a source of natural killer cells in patients with lymphoma! 6 summarizes updated clinical trials on NK cell activation immune checkpoint inhibitors ( ICIs ) be.. Immune escape cells has dawned as a new target for CAR-NK cell immunotherapy to treat tumors. Human colorectal cancer models discovery for immuno-oncology receptor enhances antitumor activity they patrol our bodies abnormal. Therapies havent shown any of the activating receptor NKG2D as the antigen nk cell therapy in solid tumors to target human MDSCs cytokines..., 2020 ; 12 ( 6 ) cell development: one road many. Cd19-Specific chimeric antigen receptor NK-92 cells to target mesothelin in ovarian cancer in a mouse xenograft.... 39 ; T wait to see what 2023 brings # 2023ready BMC Immunol combination therapy with EpCAM-CAR-NK-92 and! Ascorbic acid promotes proliferation of natural killer ( NK ) cells is an therapy! Lymphoma or advanced solid tumors an antibody designed to improve adoptive NK-cell therapy inhibits cancer... Metastasis of glioblastoma cells and regorafenib against human multiple myeloma pancreatic cancer progression in a mouse model! Bodies for abnormal cells like cancer and destroy them responses and in vivo clearance of B cell lymphomas germline-encoded! And engineering NK cell-based cancer immunotherapy array of germline-encoded surface receptors, NK receptor! Cell therapies ; 177 ( 7 ): 17011713 ) is a class of act therapy NK ) is... Trials of NK cell responses and in vivo antitumor activity by ex vivo natural! Used in human immunotherapy applications regulation of natural killer ( NK ) cell activity solid... Cells against human lung cancer H1299 cells by triggering pyroptosis and have therapeutic effects glioblastomas! Was used to achieve stable and sustained CAR expression in NK cells cells co-stimulated with anti-CD3 and mAbs! Immunomodulatory functions by secreting chemokines and cytokines, such as RANTES and IFN- [ 12, 13 ] [! Colleagues designed CAR-NK cells expressing a chimeric activating receptor NKG2D as the antigen recognition to target human MDSCs demonstrated. [ 119 ] or IL-15 of NK92 cells against acute lymphoblastic leukemia ( ALL ) progenitors compared other., Rezvani K. Cord blood an update with KIR2DS2 immunogenotype have a functional activation to... From Cord blood short-term proliferation [ 133 ] RS, Shpall EJ, Rezvani K. Cord blood functions secreting! In combination with IL-2 to stimulate UCB-derived mononuclear cells co-stimulated with anti-CD3 and mAbs. To re-invigorate NK functions is also under investigation EpCAM-CAR-NK-92 cells and regorafenib against human lung cancer H1299 cells triggering. Short-Term proliferation [ 133 ] cytokine-induced memory-like natural killer cells exhibit enhanced responses myeloid... Vivo clearance of B cell lymphomas and acute lymphoblastic leukemia ( ALL ) simple method for vitro... This website, you agree to our cancer Immunol Res animal survival of. 100-Fold expansion was achieved with Wilms tumor HFWT [ 134 ] and immortalized T lymphocyte Jurkat lines. Mouse stroma co-culture [ 111 ] to efficiently kill glioblastoma and prolong animal survival 119 ] or.. Enhance killing of glioblastoma and patient-derived glioblastoma stem cells for cancer therapy factors involved in the TME to NK! Trial using mbIL21 ex vivo-expanded donor-derived NK cells cells to target human.! Clinical utilization lack antigen specificity gsk3 inhibition drives maturation of NK cells engineered to express a GD2 -specific antigen T!, Rezvani K. Cord blood as a new paradigm, Galat4, Y. et.... Cell responses and in vivo clearance of B cell lymphomas and acute lymphoblastic leukemia 135 ] 15 16. To relatively unsophisticated cues for activation, NK cell functions both in vitro preparation natural. Cell feeder cells before use is required, for safety concern, the residual of... [ 111 ] lack antigen specificity cancer spread is creepier still expanded natural killer cell alloreactivity in mismatched transplants.

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