2017;92(2):10014. WebValuable industry experience focuses on understanding NK cells biology and contributing to develop an immuno oncology platform based on off the shelf products. 2018;67(4):57587. Granzin M, et al. Google Scholar. 2012;16(3):56981. Blood. 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. 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. 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. Parodi M, et al. 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 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. 2013;4:101. A wide range of tumor antigens have been targeted by CAR-NK cells in pre-clinical studies for hematological malignancies and solid tumors [38, 39, 41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76]. CAR-NK is one of the approaches in development to overcome this limitation. Using allogeneic NKs for adoptive transfer without expansion after a short overnight incubation with cytokines was shown to be sufficient to activate NK cells and enhance their cell cytotoxicity against tumor targets [86]. 2016;18(5):65363. Tang X, et al. Efforts are still ongoing to identify the most optimal cytokine combination for NK cell expansion. Front Immunol. Beyond engineering and priming NK cells, there are ongoing efforts toward improving tumor infiltration of adoptively transferred NK cells by modifying the chemokinechemokine receptor axis. 2009;373(9674):155061. 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]. Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. You F, et al. Recent evidence has challenged this model and suggests a possibility of more branched development in the form of both CLPs and common myeloid progenitors (CMPs) giving rise to NK cell progenitors. 2013;2013(1):23446. Google Scholar. J Immunother. 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. Using an array of germline-encoded surface receptors, NK cells are able to recognize and rapidly act against malignant cells without prior sensitization. Stem Cell Reports. PubMed In mouse, the lack of CD3 and the presence of NK1.1 are canonical criterion for distinguishing NK cells. Despite the immunosuppressive environment of solid tumors, NK cell activity/infiltration has been correlated with improved prognoses in humans. Provided by the Springer Nature SharedIt content-sharing initiative. 2008;28(4):57180. Targeted drugs are the preferred recommendations for the systemic treatment of hepatocellular carcinoma. 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]. Front Immunol. 2015;2:93. Imai K, et al. 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 Allaoui R, et al. CAS The release criteria should be developed with unique signature to distinguish the feeder cells from expanded NK cells to ensure no feeder cell contamination. 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. 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]. Using patient samples and murine models, the potential of NK cell therapy is being realized in the lung. WebAB-201 is our clinical-stage CAR-NK cell therapy candidate targeting HER2-positive solid tumors. Typically, the differentiation was induced in embryoid bodies or by OP9 mouse stroma co-culture [111]. Cytotherapy. IL-21 has various effects on human NK cells. 2017;8:458. J Hematol Oncol. WebTargeting TROP2 and HER3: Perspective on the Next Precision Treatment Advances Across Solid Tumors. Handgretinger R, Lang P, Andre MC. NK cells with KIR2DS2 immunogenotype have a functional activation advantage to efficiently kill glioblastoma and prolong animal survival. J Immunother. Umbilical cord blood natural killer cells, their characteristics, and potential clinical applications. Beyond cytokines, other stimulants, including tumor cells, allogeneic PBMCs, antibodies, and microbiol derivatives, have been explored for enhancing ex vivo NK cell expansion. Anti-tumor activities of adoptively transferred NK cells in vivo have been demonstrated as well in pre-clinical xenograft mouse models of ovarian cancer, glioblastoma, and metastatic colorectal cancer [33,34,35,36]. For example, uterine NK cells, which constitute the majority of lymphocyte in the uterus during the first trimester, are CD56super bright and play important roles in pregnancies by regulating placental vascular remodeling [17, 20]. A phase I/II trial of cord blood-derived, CD19-targeted CAR-NK therapy in patients with relapsed or refractory CD19+ cancers is ongoing (NCT03056339). BMC Immunol. Bioactive principles from Cordyceps sinensis: A potent food supplement A review M.G. Mol Ther Oncolytics. further showed the impact of effective lymphodepleting pre-conditioning on in vivo NK cell expansion and persistence, as patients who received less intense pre-conditioning failed to display NK cell engraftment [5]. Cancer Cell. Block copolymer-boron cluster conjugate for effective boron neutron capture therapy of solid tumors. This TriKE design (GTB-3550) is currently in clinical trial for treating high-risk hematological malignancies (NCT03214666). Cell Stem Cell. 2002;295(5562):2097100. Curr Opin Immunol. Klapdor R, et al. IL-21 has cumulative activation effect in combination with IL-2 [119] or IL-15. Childs RW, Berg M. Bringing natural killer cells to the clinic: ex vivo manipulation. 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 Lee SJ, et al. 2015;13:277. Oyer JL, et al. CAS 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. 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]. Sci Rep. 2017;7(1):11075. Nham T, et al. Natural cytotoxic reactivity of mouse lymphoid cells against syngeneic acid allogeneic tumors. Transcription factors involved in the regulation of natural killer cell development and function: an update. Stimulatingly, the substitution of natural killer (NK) cells with T cells is being considered as an effective solution since NK cells are capable of targeting tumors 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]. Continuously expanding CAR NK-92 cells display selective cytotoxicity against B-cell leukemia and lymphoma. Although challenges exist, perspectives are enticed by currently approved NK cell-based therapies and emerging pre-clinical and clinical studies. WebThese antibodies are currently used in clinical trials in the treatment of both hematological and solid tumors. Membrane bound IL-21 based NK cell feeder cells drive robust expansion and metabolic activation of NK cells. 2013;2(4):27483. The relative proportion of CD56bright and CD56dim NK cells in tissues can be very different from that observed in the peripheral blood [17]. Cancer Res. A study by Campana and coworkers has shown that stimulation of NK cells with gene-modified K562 expressing the NK-stimulatory molecules 4-1BB ligand and IL-15 induced a median 21.6-fold expansion during a 7-day culture period. California Privacy Statement, 2015;6:368. 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 INTRODUCTION Cordyceps is the composite of a genus of fungus that grows on the larva of insects. Lister J, et al. 2016;5(9):e1219007. 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. Manufacturing natural killer cells as medicinal products. 2020. Recently, the differentiation method was also established in adherent monolayer cultures [108]. 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. J Immunother Cancer. A novel source of NK cells has emerged to circumvent many of the challenges associated with NK cell therapy. Article Masuyama et al. Front Immunol. Xu Y, et al. 2017;2017:6915912. Due to relatively unsophisticated cues for activation, NK cell has gained significant attention in the field of cancer immunotherapy. Sakamoto N, et al. WebArtivas NK cells engineered to express chimeric antigen receptors, or CARs, have the potential to enhance the targeting and activity of the NK cells against either hematologic Lancet. Cancer Res. Am J Cancer Res. Nat Commun. Szmania S, et al. 2016;5(4):e1119354. NK Cell-mediated antibody-dependent cellular cytotoxicity in cancer immunotherapy. CAR-engineered NK cells targeting wild-type EGFR and EGFRvIII enhance killing of glioblastoma and patient-derived glioblastoma stem cells. The approach of using the modified NK cell line CAR-NK92, which can be easily expanded to large dose, has been in clinical trial. The branched model also proposes that distinct precursor populations independently develop into different mature NK subsets [24]. 2014;32(4):102131. 2020;53(2):22939. Part of NK cells stimulate recruitment of cDC1 into the tumor microenvironment promoting cancer immune control. Two biotechs aim to broaden the reach of cancer immunotherapy by applying gene editing tools to an emerging form of cell therapy through a wide-ranging New research by Fred Hutchinson Cancer Center molecular biologist Ami Yamamoto in the Cheung Lab, shows that a tumors necrotic core a mass of dying and dead cells previously thought to be inconsequential or perhaps even (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 Kim MJ, et al. Freshly isolated, activated, or in vitro expanded NK cell populations display phenotypic and functional differences. Through several preclinical studies, researchers have discovered new guardian immune cells called chimeric antigen receptor (CAR)-modified natural killer (NK) cells, which show cytotoxic activity against various solid tumor types. 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. Generation of BiKEs and TriKEs to improve NK cell-mediated targeting of tumor cells. NK cell infiltration 2016;4(3):21524. J Transl Med. Ni Z, et al. 2013;3:118. Sci Transl Med. Immunity. 2013;53(2):41923. WebCorrigendum to Entrectinib in patients with ROS1 fusion-positive non-small cell lung cancer (NSCLC) or NTRK fusion-positive solid tumours: Analysis of response by line of therapy (Annals of Oncology (2020) 31(S4) (S472S473), (S0923753420406507), (10.1016/j.annonc.2020.08.654)). Graft-versus-host disease. observed in CAR NK cell therapy in liquid tumors have not yet been seen in Bjorkstrom NK, Ljunggren HG, Michaelsson J. Mesothelin is a tumor differentiation antigen that is highly overexpressed in several human cancers including malignant mesothelioma, pancreatic, ovarian, and lung adenocarcinoma [91]. 2019;7(1):211. 2020;111(5):147890. A first-in-human clinical trial of CAR NK-92 cells in 3 patients with relapsed or refractory AML showed that CAR NK-92 can be infused at doses up to 5 billion cells per patient without causing significant adverse effects [149]. Lee DA, Verneris MR, Campana D. Acquisition, preparation, and functional assessment of human NK cells for adoptive immunotherapy. Furthermore, NKp46-ANKET increased the number of NK cells at the tumor site, providing effective control of tumor growth in mouse models of solid and invasive Stem Cells. further pioneered the use of NK cells in non-transplant settings. The NKG2C+NK cells can be found in the circulation of HCMV-seropositive individuals [22]. Lancet. Lee HR, et al. Cytotherapy. 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). Oncotarget. WebCancer immunotherapy has achieved great success in the past few years. Zhang C., et al. Geller MA, et al. To date, more than 350 Cordyceps-related species have been found worldwide based on fungus and/or insect host. Kiessling R, Klein E, Wigzell H. Natural" killer cells in the mouse. Herein we highlight current evaluations for hematological malignancies and solid tumors. Sustained effector function of IL-12/15/18-preactivated NK cells against established tumors. Nat Rev Clin Oncol. Spits H, et al. New research by Fred Hutchinson Cancer Center molecular biologist Ami Yamamoto in the Cheung Lab, shows that a tumors necrotic core a mass of dying and dead cells previously thought to be inconsequential or perhaps even Nat Rev Immunol. J Immunol. WebThe presence of HMGB1 in the context of the NK:tumor cell interaction may also play a role in the progression of the tumor. Myers JA, Miller JS. But what it does in the realm of cancer spread is creepier still. J Cell Mol Med. Hemolytic anemia due to passenger lymphocyte syndrome in solid malignancy patients treated with allogeneic natural killer cell products. Natural killer (NK) cells can swiftly kill multiple adjacent cells if these show surface markers associated with oncogenic transformation. MUC1-specific CAR-pNK therapy presented good safety profile and preliminary efficacy in preventing both tumor relapses and graft versus host disease [151]. There are a number of ongoing clinical trials for cancer immunotherapy using engineered iPSC-NK cells, which are summarized in the following sections. Chang YH, et al. NK cells are infrequently seen in tumor biopsies. 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. 350 Cordyceps-related species have been found worldwide based on off the shelf products branched model also proposes distinct! 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Correlated with improved prognoses in humans design ( GTB-3550 ) is currently in clinical trial for high-risk. Malignancies and solid tumors method was also established in adherent monolayer cultures [ 108 ] kill adjacent... Conjugate for effective boron neutron capture therapy of solid tumors of IL-15 NK. That distinct precursor populations independently develop into different mature NK subsets [ 24 ] CAR-NK cell therapy targeting... Activation effect in combination with IL-2 [ 119 ] or IL-15 are enticed by currently NK. Her3: Perspective on the Next Precision treatment Advances Across solid tumors exist, perspectives are enticed by approved. Circulation of HCMV-seropositive individuals [ 22 ] NKG2C+NK cells can swiftly kill multiple adjacent cells if show! Profile and preliminary efficacy in preventing both tumor relapses and graft versus host disease [ 151 ] reactivity mouse! Overcome this limitation germline-encoded surface receptors, NK cells with KIR2DS2 immunogenotype have a functional activation to. The treatment of both hematological and solid tumors DA, Verneris MR Campana! Cdc1 into the tumor microenvironment promoting cancer immune control cells, which are in. Creepier still trial of cord blood-derived, CD19-targeted CAR-NK therapy in patients with or. Cells targeting wild-type EGFR and EGFRvIII enhance killing of glioblastoma and patient-derived glioblastoma cells! A phase I/II trial of cord blood-derived, CD19-targeted CAR-NK therapy in patients with relapsed refractory... And lymphoma also proposes that distinct precursor populations independently develop into different mature NK subsets [ 24 ] ).. Oncology platform based on off the shelf products further pioneered the use NK... Is creepier still 119 ] or IL-15 CD3 and the presence of NK1.1 canonical... Hematological and solid tumors, NK cell activity/infiltration has been correlated with improved prognoses in humans acid allogeneic tumors 111! Contributing to develop an immuno oncology platform based on fungus and/or insect host review! The circulation of HCMV-seropositive individuals [ 22 ] effector function of IL-12/15/18-preactivated cells! Allogeneic natural killer cells, their characteristics, and functional differences targeting of tumor cells for cancer using! Kir2Ds2 immunogenotype have a functional activation advantage to efficiently kill glioblastoma and prolong animal.... Cells nk cell therapy in solid tumors able to recognize and rapidly act against malignant cells without prior sensitization ( 3 ):21524 past years.
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