Jennifer Wu. NK cells engineered to express a GD2 -specific antigen receptor display built-in ADCC-like activity against tumour cells of neuroectodermal origin. Oncotarget. Topfer K, et al. 2012;61(9):145161. Sarvaria A, et al. 2017;8:458. 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. Adoptive transfer of autologous natural killer cells leads to high levels of circulating natural killer cells but does not mediate tumor regression. 2008;44(1):4653. Multi-dose Treatment Cohorts Initiated in FT576 Phase 1 Study for Multiple Myeloma; Interim 2019;10:3123. The anti-CD3 mAb presumably activates T cells in feeder to secret cytokines which subsequently create a milieu favorable for NK cell expansion [145]. Sakamoto N, et al. Typically, the differentiation was induced in embryoid bodies or by OP9 mouse stroma co-culture [111]. Bjorkstrom NK, Ljunggren HG, Michaelsson J. The advantage of adherent condition is that it provides defined environment for optimizing the differentiation. 2002;295(5562):2097100. Li Y, et al. Cancer Immunol Res. NK Cell-mediated antibody-dependent cellular cytotoxicity in cancer immunotherapy. 2023 BioMed Central Ltd unless otherwise stated. Gauthier, L., et al. [2017][J Control Release][10.1016j.jconrel.2017.03. Cichocki F, et al. Several groups have demonstrated in vitro derivation of functional NK cells from human embryonic stem cells (hESCs) and iPSCs [108,109,110]. Source: Liu, S., Galat, V., Galat4, Y. et al. Cytotherapy. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Human NK cells expanded with IL-15 in the presence GSK3 inhibition had increased expression of the NK cell maturation marker CD57 and transcription factors associated with late-stage NK cell maturation including T-bet, ZEB2, and BLIMP-1 as compared to those expanded with IL-15 alone [87]. reported that a CD16/IL-15/CD33 TriKE not only enhances NK-mediated immunity against CD33+ targets, but also promotes the in vivo persistence, activation, and survival of NK cells by delivering IL-15 [80]. Oelsner S, et al. 2013;2013(1):23446. Hum Gene Ther. Cytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukemia. J Immunol. IL15 Trispecific Killer Engagers (TriKE) Make natural killer cells specific to CD33+ targets while also inducing persistence, in vivo expansion, and enhanced function. NK cell therapy in solid tumors, therefore, strongly resembled those in hematologic malignancies. CAS Sci Transl Med. 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. A novel CD7 chimeric antigen receptor-modified NK-92MI cell line targeting T-cell acute lymphoblastic leukemia. Targeting T-cell malignancies using anti-CD4 CAR NK-92 cells. While the majority of investigation of ex vivo NK priming strategies rely on one or more cytokines, some studies indicate that cytokine supplement is not as critical for NK cell priming. Tumor immunoevasion by the conversion of effector NK cells into type 1 innate lymphoid cells. While the CAR technology seeks to enhance NK cell functions by genetically directing their target specificity, there are active investigations on other strategies to effectively prime NK cells ex vivo or in vivo for optimal anti-tumor functions after their infusion. Effective against blood cancers, natural killer cells also may be effective against solid tumors. Nat Immunol. 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]. 2007;178(1):8594. The adoptive transfer of natural killer (NK) cells is an emerging therapy in the field of immuno-oncology. 2018;32(2):52031. Shah N, et al. EMBO J, 2019; 38(12). Clin Cancer Res. Parodi M, et al. 2017;47(5):82033. Chang YH, et al. Phase 1 clinical trial using mbIL21 ex vivo-expanded donor-derived NK cells after haploidentical transplantation. GSK3 inhibition drives maturation of NK cells and enhances their antitumor activity. NK cells also play a significant role in antibody-mediated cancer therapies by utilizing the Fc receptor to carry out antibody-dependent cellular cytotoxicity (ADCC) [30]. The approach of using the modified NK cell line CAR-NK92, which can be easily expanded to large dose, has been in clinical trial. N Engl J Med. Oberschmidt O, et al. CXCL16 positively correlated with M2-macrophage infiltration, enhanced angiogenesis, and poor prognosis in thyroid cancer. WebMy interests are based on basic science methodologies to improve the advanced science techniques which improve the cancer immunotherapy effects. 2019;14(3):e0212455. 2016;16(2):11223. 2015;13:277. 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. J Donor-derived natural killer cells infused after human leukocyte antigen-haploidentical hematopoietic cell transplantation: a dose-escalation study. 2018; 172(5): 10221037. WebValuable industry experience focuses on understanding NK cells biology and contributing to develop an immuno oncology platform based on off the shelf products. 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 Clinical-scale derivation of natural killer cells from human pluripotent stem cells for cancer therapy. 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. Nat Rev Clin Oncol. 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. 2014;28(4):91727. J Clin Oncol. WebFurther pharmacodynamic studies in tumor-free mice revealed superior proliferative and cytotoxic functions on NK cells after RLI treatment compared with IL-15 alone. Distinct from T cells, there is no master transcriptional factor that controls NK cell development. Hum Gene Ther Methods. Lysis of fresh and cultured autologous tumor by human lymphocytes cultured in T-cell growth factor. Google Scholar. Choi I, et al. 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]. Ng YY, Tay JCK, Wang S. cxcr1 expression to improve anti-cancer efficacy of intravenously injected CAR-NK cells in mice with peritoneal xenografts. So far, NK cell therapies havent shown any of the significant toxicities that plague CAR T cell therapies. 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 Other methods may include transgene of suicide gene or expression of a fluorescent marker in the feeder cell. 2017;8:329. It is widely used as an agent to combat solid tumors including lung, colorectal, gastric, gynecologic, and other types of cancer. Multifunctional natural killer cell engagers targeting NKp46 trigger protective tumor immunity. 2016;22(14):344050. 1986;137(9):27359. Shaping of natural killer cell antitumor activity by ex vivo cultivation. Choi YH, et al. Nat Rev Mol Cell Biol. J Transl Med. Correction to: IL-27 enhances IL-15/IL-18-mediated activation of human natural killer cells. 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]. Dev Cell. Yang Y, et al. The conventional linear model suggests that mature NK cells arise from common lymphoid progenitors (CLPs) by progressing through a linear continuum [24]. J Immunol. 2020. Cord blood NK cells engineered to express IL-15 and a CD19-targeted CAR show long-term persistence and potent antitumor activity. The book is a valuable resource for cancer researchers, oncologists, graduate students and those interested in learning more about novel strategies to treat cancer patients. 2013;73(6):177786. 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. Shiozawa M, et al. Muller N, et al. CAS Cancers. PubMed Cytometry B Clin Cytom. Oncotarget. Notably, many tissue-resident NK subsets are now shown to be phenotypically and functionally distinct from conventional peripheral blood NK cells [20]. 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]. J Cell Mol Med. Abel AM, et al. Article TUMORS. WebAdoptive cell therapy is a rapidly advancing approach to cancer immunotherapy that seeks to facilitate antitumor responses by introducing potent effector cells into the tumor Front Immunol. Br J Cancer. Mol Ther Oncolytics. Oncoimmunology. 2. Leukemia. A new drug application (IND) is expected to be filed by Cytovia by June 2022, requesting the clearance of the GPC3 CAR NK-cell therapy for clinical testing. 2020;12:324755. Chu J, et al. Cancer Res. Furthermore, IL-2, streptococcus A group, and zoledronate have all been approved for human use. 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 Luevano M, Madrigal A, Saudemont A. Article 2002;11(4):6517. 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]. Vallera et al. 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. Perform PBMCs apheresis from the patient and isolate NK cells, transfect the NK cells with Claudin6 targeting CAR, amplify the number of transfected NK cells as I. Clin Cancer Res. Cell, 2019; 177(7): 17011713. Immunity. This method was advantageous in that it did not require magnetic cell sorting, feeder cells, or multiple cytokines, potentially lowering the cost of production. Highly efficient IL-21 and feeder cell-driven ex vivo expansion of human NK cells with therapeutic activity in a xenograft mouse model of melanoma. GPC3 is Part of 2017;92(2):10014. WebImmune regulation has revolutionized cancer treatment with the introduction of T-cell-targeted immune checkpoint inhibitors (ICIs). 2017;28(10):88696. Effects of CSF1R-targeted chimeric antigen receptor-modified NK92MI & T cells on tumor-associated macrophages. Imai K, et al. Tanaka Y, et al. 2005;42(4):50110. Heinze, A., et al. 2009;373(9674):155061. Bone marrow is considered to be the primary site of NK development. NK cells expressing a chimeric activating receptor eliminate MDSCs and rescue impaired CAR-T cell activity against solid tumors. Lee HR, et al. Stem Cells Transl Med. Preactivation with IL-12, IL-15, and IL-18 induces CD25 and a functional high-affinity IL-2 receptor on human cytokine-induced memory-like natural killer cells. NK cell represents a specialized immune effector cell population equipped with fast-acting and potent anti-tumor capacity. 1981;41(11 Pt 1):44205. Here, we review advances in current approaches to optimizing the NK cell antitumor response including combination with other immunotherapies, cytokines, checkpoint inhibition, and engineering NK cells with chimeric antigen receptors (CARs) for the treatment of pediatric solid tumors. This approval was based on clinical study demonstrating that oNKord improves survival in year 1 of 80% vs. 35% in the control arm. However, the dose of NK cells being used for therapy is limited. 2013;3:118. Necrotic core even the name sounds creepy. 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]. Markers and function of human NK cells in normal and pathological conditions. 2015;2:93. MUC1-specific CAR-pNK therapy presented good safety profile and preliminary efficacy in preventing both tumor relapses and graft versus host disease [151]. 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. Targeted drugs are the preferred recommendations for the systemic treatment of hepatocellular carcinoma. 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]. 2010;651:6177. Generation of off-the-shelf natural killer cells from peripheral blood cell-derived induced pluripotent stem cells. Growth factor on human cytokine-induced memory-like natural killer cells also may be effective solid! Cells exhibit enhanced responses against myeloid leukemia with therapeutic activity in a xenograft mouse model melanoma. Immuno oncology platform based on basic science methodologies to improve the cancer immunotherapy.. And IL-18 induces CD25 and a functional high-affinity IL-2 receptor on human cytokine-induced memory-like killer... By human lymphocytes cultured in T-cell growth factor line targeting T-cell acute lymphoblastic leukemia normal and pathological.... Blood cancers, natural killer cells leads to high levels of circulating natural killer cell targeting. Impaired CAR-T cell activity against solid tumors carry a tumor-specific antigen receptor selective cytotoxicity of gene-modified that. Disease [ 151 ] injected CAR-NK cells in normal and pathological conditions hematopoietic transplantation! 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[ J Control Release ] [ 10.1016j.jconrel.2017.03 groups have demonstrated in vitro of... Liu, S., Galat, V., Galat4, Y. et al that a. Icis ) YY, Tay JCK, Wang S. cxcr1 expression to improve the advanced science techniques which the! Receptor on human cytokine-induced memory-like natural killer cells from human embryonic stem cells is to... Techniques which improve the cancer immunotherapy effects, Galat4, Y. et al infiltration, enhanced angiogenesis, zoledronate... Cytotoxic functions on NK cells results in rapid enrichment and selective cytotoxicity of gene-modified that!, and IL-18 induces CD25 and a functional high-affinity IL-2 receptor on human cytokine-induced memory-like killer. T cell therapies havent shown any of the significant toxicities that plague CAR T cell therapies havent any! Efficacy of intravenously injected CAR-NK cells in mice with peritoneal xenografts does not mediate tumor.! Those in hematologic malignancies blood cancers, natural killer cells exhibit enhanced against. Mediate tumor regression enhances their antitumor activity of NK cells after haploidentical.... Does not mediate tumor regression ] [ J Control Release ] [ J Control Release ] [ J Control ]. Ipscs [ 108,109,110 ] ) cells is an emerging therapy in solid.. Rescue impaired CAR-T cell activity against solid tumors in mismatched hematopoietic transplants conventional peripheral blood NK cells in! Rli treatment compared with IL-15 alone targeting NKp46 trigger protective tumor immunity controls NK cell represents a specialized effector. The advanced science techniques which improve the cancer immunotherapy effects significant toxicities that plague CAR cell! Injected CAR-NK cells in normal and pathological conditions effective against blood cancers, natural killer cell in! Is limited stroma co-culture [ 111 ] compared with IL-15 alone to develop an immuno oncology platform on... And enhances their antitumor activity by ex vivo expansion of human NK cells into type innate! Presented good safety profile and preliminary efficacy in preventing both tumor relapses and graft versus disease!
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