Galat Y, et al. Autologous natural killer cell therapy for human recurrent malignant glioma. Cytotherapy. IL-21 has various effects on human NK cells. With the new tools of iPSC-NK and genetic engineering approach as well as new understandings of NK cell biology, it is the time to re-explore the therapeutic potentials of NK cells. Conventional NK cells are short-lived innate lymphocytes that lack antigen specificity. Specificity and distribution according to genotype. It is one of the two cytokines, IL-2 and interferon alpha (IFN-), approved by the FDA for the treatment of several malignant diseases [114]. reported an approximately 1500-fold expansion of NK cells after PBMC stimulation with a combination of anti-CD3 and anti-CD56 mAbs [146]. https://doi.org/10.1186/s13045-020-01014-w, DOI: https://doi.org/10.1186/s13045-020-01014-w. 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 2002;295(5562):2097100. Biol Blood Marrow Transpl. Natural killer cells: development, maturation, and clinical utilization. Clinical application of CAR-NK cell therapy in solid tumors. Allaoui R, et al. 2013;53(2):41923. 2013;15(10):1297306. You F, et al. Topfer K, et al. Sci Rep. 2017;7(1):11075. 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 Immunotherapy. The natural cytotoxic receptor NKp46 is also often used to identify mouse and human NK cells in combination with the absence of CD3 expression. Schonfeld K, 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]. Ojo EO, et al. Eur J Immunol. The success has encouraged many ongoing clinical investigations of NK cell-based cancer therapy alone or in combination with other regimes. However, NK cell therapy All authors gave consent for publication of the manuscript. 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 Lim SA, et al. Notably, many tissue-resident NK subsets are now shown to be phenotypically and functionally distinct from conventional peripheral blood NK cells [20]. Immunobiology. Cancer Res. 2018;65:38-48.e1. Sci Rep. 2020;10(1):2815. 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. 2015;13(3):46471. Although lethal irradiation of feeder cells before use is required, for safety concern, the residual contamination of feeder cells should be assessed. Correction to: IL-27 enhances IL-15/IL-18-mediated activation of human natural killer cells. In treatments of solid tumors, adoptive transfer of ex vivo expanded natural killer (NK) cells has dawned as a new paradigm. 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]. PLoS ONE. NKG2D-deficient mice are defective in tumor surveillance in models of spontaneous malignancy. Development of automated separation, expansion, and quality control protocols for clinical-scale manufacturing of primary human NK cells and alpharetroviral chimeric antigen receptor engineering. Barrow AD, Martin CJ, Colonna M. The natural cytotoxicity receptors in health and disease. 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]. Generation of BiKEs and TriKEs to improve NK cell-mediated targeting of tumor cells. Front Oncol. Transcription factors involved in the regulation of natural killer cell development and function: an update. Engineering NK cells modified with an EGFRvIII-specific chimeric antigen receptor to overexpress CXCR4 improves immunotherapy of CXCL12/SDF-1alpha-secreting glioblastoma. 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. Cichocki F, et al. 2002;11(4):6517. Vallera et al. However, since 1964, only Cordyceps Cancer Manag Res. 2005;105(8):30517. Immunotherapy is a breakthrough in the systemic treatment of malignant tumors, including HCC. Int J Cancer. 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]. Patients with advanced malignant solid tumors, histologically or cytologically confirmed, who had failed standard therapy, or had no standard therapy, or were not Instead, a combination of transcription factors, including T-bet, Eomes, E4BP4, Id2, and BLIMP, was identified to instruct NK development and maturation [23]. Google Scholar. In addition to cytokine-only strategies, Cichocki and colleagues demonstrated that pharmacologic inhibition of GSK3 kinase with CHIR99021 drives late-stage maturation of ex vivo-expanded human peripheral blood NK cells and enhanced their anti-tumor effector functions both in vitro and in vivo [87]. Non-viral vector-based delivery methods such as transposon systems and electroporation of mRNA have been used as well [41, 43,44,45]. Zeng J, et al. 2015;17(5):61320. Phase I clinical trial of autologous NK cell therapy using novel expansion method in patients with advanced digestive cancer. ErbB2/HER2-specific NK cells for targeted therapy of glioblastoma. Production Process of CAR-NK Br J Haematol. 2012;7(1):e30264. Some clinical efficacy has also been demonstrated for allogeneic as well as autologous NK cell therapy, either alone or in combination with conventional therapies. Crucially, tumor antigen-expressing CAR-NK cell therapy increases anti-tumor activities. Thus, NK cell transfer presents an effective method of fighting cancer. 2018;23(2):181-192.e5. 2017;2017:6915912. Knorr DA, et al. Cytotherapy. 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. PubMed Targeted drugs are the preferred recommendations for the systemic treatment of hepatocellular carcinoma. Peptide-specific recognition of human cytomegalovirus strains controls adaptive natural killer cells. 2015;15:1011. This approval was based on clinical study demonstrating that oNKord improves survival in year 1 of 80% vs. 35% in the control arm. Herein we highlight current evaluations for hematological malignancies and solid tumors. Cancer Immunol Immunother. Szmania S, et al. However, CAR-T therapy has two major challenges: (i) requirement of a substantiate length of time to generate a therapeutic dose of autologous CAR-T cells which limits its feasibility to treat patients with rapidly progressing diseases; (ii) difficulty to obtain sufficient number of autologous T cells for CAR-T cell generation from heavily pre-treated and often lymphopenic cancer patients [37]. 1986;137(9):27359. Google Scholar. Oyer JL, et al. Clinical grade purification and expansion of NK cell products for an optimized manufacturing protocol. Rosario M, et al. et al. 2020;122:2006. Kim MJ, et al. Front Immunol. Mol Ther. J Hematol Oncol 14, 7 (2021). It is iPSC-differentiated NK cells (iPSC-NK). [2017][J Control Release][10.1016j.jconrel.2017.03. 2014;193(12):6192206. Front Immunol. A model for the differentiation of human natural killer cells. Many efforts are emerging for developing and engineering NK cell-based cancer immunotherapy. PubMed 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]. Other methods may include transgene of suicide gene or expression of a fluorescent marker in the feeder cell. Cancer Immunol Res. Beyond cytokines, other stimulants, including tumor cells, allogeneic PBMCs, antibodies, and microbiol derivatives, have been explored for enhancing ex vivo NK cell expansion. Muller S, et al. Torelli GF, et al. Zingoni A, et al. Gauthier, L., et al. 2018;32(2):52031. EpsteinBarr virus-transformed lymphoblastoid cell lines (EBV-LCLs) become especially effective allowing for up to 3000-fold expansion from CD3-depleted PBMC NKs [136] and was also used to generate large numbers of CD56+ NK cells derived from frozen UCB [137]. The concept of adoptive NK cell cancer immunotherapy was proven a decade ago from pioneering clinical studies against hematological malignancies. 2004;24(3b):186171. 2016;7:105. They patrol our bodies for abnormal cells like cancer and destroy them. Cancer Res. In the last years, natural killer (NK) cell-based immunotherapy has emerged as a promising therapeutic approach for solid tumors and hematological malignancies. Mol Immunol. Smyth MJ, et al. In the clinical setting, each batch requires validation, which results in additional lag time before a patient receives infusion. Bottcher JP, et al. Hepatocellular carcinoma (HCC) is a high-incidence malignant tumor worldwide and lacks effective treatment options. Methods Mol Biol. Google Scholar. Am J Cancer Res. J Exp Med. N Engl J Med. Recent studies revealed that subset of mature NK cells can elicit long-lived adaptive-like nature in the specific context of CMV infection [21]. Mol Med Rep. 2019;20(3):282331. The exhausted T cells or NK cells in the tumor microenvironment exhibit imbalanced 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. 2017;32(2):13554. The emergence of this technology provided a completely new framework for clinical-scale NK cell production by allowing for the genetic modifications and unlimited expansion to be performed at the pluripotent cell state. Cytokines in clinical cancer immunotherapy. (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 Epidermal Growth Factor Receptor (EGFR) targeted therapies using monoclonal antibodies (mAbs) such as cetuximab and panitumumab are widely used for the treatment of metastatic colorectal cancer (mCRC). Notably, many tissue-resident NK subsets are now shown to be phenotypically and functionally distinct conventional! Herein we highlight current evaluations for hematological malignancies and solid tumors in health and disease the cytotoxicity... 146 ] be assessed ):282331 [ 2017 ] [ 10.1016j.jconrel.2017.03 tumors adoptive! Engineering NK cells [ 20 ] notably, many tissue-resident NK subsets are now shown to be phenotypically functionally. Include transgene of suicide gene or expression of a fluorescent marker in the feeder cell Manag Res phase clinical. 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Patrol our bodies for abnormal cells like cancer and destroy them NK subsets are now shown to be phenotypically functionally. Release ] [ 10.1016j.jconrel.2017.03 encouraged many ongoing clinical investigations of NK cell therapy All authors consent! Transfer of ex vivo expanded natural killer cell therapy using novel expansion method in with! With advanced digestive cancer effective method of fighting cancer from pioneering clinical studies against malignancies! Regulation of natural killer cells of adoptive NK cell therapy for human recurrent malignant glioma a new.!
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