With the understanding of how NK cells are activated, the initial NK cell-based therapy was pioneered in the clinical setting of hematopoietic stem cell transplants (HSCTs) whereby NK cells were shown to have the capacity to exert a graft versus leukemia effect. The anti-tumor response of LAK cells was shown attributed mainly to NK cells [116]. Initial successes of adoptive NK cell transfer in treating hematological cancers prompted clinical endeavors in using the strategy against solid cancers. 2017;32(2):13554. Jennifer Wu supervised the study. One approach to address the safety concern is the use of lysed cell product. However, there are many challenges to overcome, such as difficulty to meet clinical-grade ex vivo expansion, limited in vivo persistence, limited infiltration to solid tumors, and tumor editing to evade NK cell activity. Synergistic effects of cabozantinib and EGFR-specific CAR-NK-92 cells in renal cell carcinoma. Immunotherapy is a breakthrough in the systemic treatment of malignant tumors, including HCC. Huijskens MJ, et al. 2016;18(5):65363. CAR-engineered iPSC-NK cells already have demonstrated effectiveness in targeting human tumors in preclinical studies [41]. 2005;42(4):50110. Despite the immunosuppressive environment of solid tumors, NK cell activity/infiltration has been correlated with improved prognoses in humans. 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. 2013;73(6):177786. Lim SA, et al. Topfer K, et al. Natural killer cells: definition of a cell type rather than a function. Genetically engineered CAR NK cells display selective cytotoxicity against FLT3-positive B-ALL and inhibit in vivo leukemia growth. CAR-NK is one of the approaches in development to overcome this limitation. Chang YH, et al. Lee J, et al. Membrane bound IL-21 based NK cell feeder cells drive robust expansion and metabolic activation of NK cells. 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. NK cells are cytotoxic against a wide range of tumor cells of solid cancer types in vitro. Terms and Conditions, J Immunol. Bjorkstrom NK, Ljunggren HG, Michaelsson J. Xu Y, et al. WebTargeting TROP2 and HER3: Perspective on the Next Precision Treatment Advances Across Solid Tumors. Google Scholar. Innate lymphoid cells: a proposal for uniform nomenclature. Phillips JH, Lanier LL. T cells equipped with CARs have been shown to provide clinical benefit for patients with select liquid cancers. Some investigations have sought to enhance NK migration toward the tumor by genetically modifying NK cells to overexpress chemokine receptors [54, 59, 94]. 2004;24(3b):186171. Stem Cell Reports. Parihar and colleagues designed CAR-NK cells expressing the activating receptor NKG2D as the antigen recognition to target human MDSCs. Denman CJ, et al. Blood. 2016;7:504. 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]. 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]. Sizhe Liu, Vasiliy Galat, Yekaterina Galat, Yoo Kyung Annie Lee, Derek Wainwright, and Jennifer Wu wrote and reviewed the manuscript. statement and 2015;2:93. Tri-functional NK cell engagers (NKCEs), which crosslink both NKp46 and CD16, have demonstrated superior in vitro and in vivo anti-tumor activities compared to conventional monoclonal antibodies targeting the same antigens [81]. 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 J Immunol. 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]. Phase 1 clinical trial using mbIL21 ex vivo-expanded donor-derived NK cells after haploidentical transplantation. 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. Phase I study of cord blood-derived natural killer cells combined with autologous stem cell transplantation in multiple myeloma. Article [2017][J Control Release][10.1016j.jconrel.2017.03. Cancer Res. Clinicaltrials.gov currently lists over 100 clinical trials of NK cell-based cancer immunotherapy. 2017;8:329. Dual targeting of glioblastoma with chimeric antigen receptor-engineered natural killer cells overcomes heterogeneity of target antigen expression and enhances antitumor activity and survival. (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 The mechanism of CTV-1-mediated NK priming is unclear. 2018;6(1):136. 2017;8:458. Phase I clinical trial of autologous NK cell therapy using novel expansion method in patients with advanced digestive cancer. Hematology Am Soc Hematol Educ Program. Characterization of the maturation stage of NK cells demonstrated that RLI favored accumulation of CD11b+ CD27high KLRG1+ Can't wait to see what 2023 brings #2023ready Clin Cancer Res. Recent observations show that HMGB1 is a potent driver CAR NK therapy offers experimental treatment option for blood cancers BY Devon Carter Natural killer cells or NK cells are part of our immune system. 2017;47(5):82033. Other methods may include transgene of suicide gene or expression of a fluorescent marker in the feeder cell. Studies on the in vitro activation of Leu-11+ granular lymphocytes with a natural killer-sensitive tumor cell, K562. Veluchamy JP, et al. 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. It is widely used as an agent to combat solid tumors including lung, colorectal, gastric, gynecologic, and other types of cancer. Role of natural killer cell alloreactivity in HLA-mismatched hematopoietic stem cell transplantation. Mol Immunol. The exciting results from Liu et al. The following section summarizes the current pre-clinical efforts to enhance the efficacy of NK cell-based therapy. Ex vivo expansion of highly cytotoxic human NK cells by cocultivation with irradiated tumor cells for adoptive immunotherapy. et al. A clinically adaptable method to enhance the cytotoxicity of natural killer cells against B-cell malignancies. The advantage of adherent condition is that it provides defined environment for optimizing the differentiation. Lotze MT, et al. NK cell represents a specialized immune effector cell population equipped with fast-acting and potent anti-tumor capacity. Kim EK, et al. 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. Iliopoulou EG, et al. 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]. 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]. 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]. 2013;4:101. Roda JM, et al. Similar to CAR-T cells, CAR-NK cells are genetically modified to express CARs that recognize a specific antigen uniquely expressed or overexpressed by target cells. The antigen recognition domain usually consists of a single-chain fragment (scFV) molecule derived from a monoclonal antibody, and nanobody-based constructs have been used in limited studies to date [72]. IL15 Trispecific Killer Engagers (TriKE) Make natural killer cells specific to CD33+ targets while also inducing persistence, in vivo expansion, and enhanced function. 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. Clin Cancer Res. For hematological cancers, CD19 remains a major target. 2005;105(8):30517. Rosario M, et al. Front Immunol. Google Scholar. Int J Cancer. Methods Mol Biol. Development of cMET-specific chimeric antigen receptor-engineered natural killer cells with cytotoxic effects on human liver cancer HepG2 cells. Block copolymer-boron cluster conjugate for effective boron neutron capture therapy of solid tumors. Leukemia. An even greater expansion of NK cells, of over 30,000-fold in a period of 3weeks, was achieved with K562 membrane-bound IL-21 and 4-1BB ligand [127,128,129,130]. 2017;25(8):176981. Table 6 summarizes updated clinical trials of NK cell-based therapy for all solid tumors. Due to relatively unsophisticated cues for activation, NK cell has gained significant attention in the field of cancer immunotherapy. 2016; 8(357): p. 357ra123. 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]. Zhang Q, et al. The NKG2D-2B4 containing CAR-NK had elevated Syk and Erk1/2 phosphorylation [42]. Cancer Res. It is believed that membrane-bound interleukins are able to stimulate the expansion of NK cells more effectively than the soluble form. 2019;145(7):193545. Google Scholar. NK Cells of the Lung 2010;28(6):9559. 2023 BioMed Central Ltd unless otherwise stated. Ascorbic acid promotes proliferation of natural killer cell populations in culture systems applicable for natural killer cell therapy. 2017;9(6):1796812. Use of chimeric antigen receptor NK-92 cells to target mesothelin in ovarian cancer. Szmania S, et al. demonstrated a more than 500-fold NK expansion with over 98% purity within 2weeks and a greater than 5000-fold NK expansion over a 3-week period [147]. 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. With the subcutaneous hypopharyngeal tumor xenograft model, it was shown that CXCR1-expressing CAR-NK cells had enhanced tumor infiltration and tumor control as compared to control CAR-NK cells [54]. Manage cookies/Do not sell my data we use in the preference centre. The trial is Natural killer cells produce T cell-recruiting chemokines in response to antibody-coated tumor cells. Despite the immunosuppressive environment of solid tumors, NK cell activity/infiltration has been correlated with improved prognoses in humans. Wang J, et al. 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]. PubMed Central Cancer Immunol Immunother. 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 Markers and function of human NK cells in normal and pathological conditions. Hemolytic anemia due to passenger lymphocyte syndrome in solid malignancy patients treated with allogeneic natural killer cell products. Retargeting of natural killer-cell cytolytic activity to ErbB2-expressing cancer cells results in efficient and selective tumor cell destruction. NK cells, which were discovered almost 50 years ago, can defend against tumors in most tissues without requiring detection of specific tumor antigens. Based on the pre-clinical findings, CTV-1 lysate-primed human NK cells (CNDO-109-NK cells) derived from HLA-haploidentical donors were evaluated for safety in a phase I clinical trial (NCT01520558) in high-risk AML patients with AML after first complete remission [89]. WebNK cells are innate lymphocytes holding a spectrum of functional aptitudes, comprising anti-cancer, anti-viral, and anti-graft-versus-host disease (GVHD) functions ( 2 ). MUC1-specific CAR-pNK therapy presented good safety profile and preliminary efficacy in preventing both tumor relapses and graft versus host disease [151]. The natural cytotoxic receptor NKp46 is also often used to identify mouse and human NK cells in combination with the absence of CD3 expression. Lanier LL, et al. Production Process of CAR-NK 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. The umbilical cord blood (UCB) [102,103,104,105] or placenta [106] represents other notable sources of NK cells that have been pursued for clinical applications. So far, NK cell therapies havent shown any of the significant toxicities that plague CAR T cell therapies. Zhang P, et al. Cichocki F, et al. Chapter 5 Cordyceps as an Herbal Drug Bao-qin Lin and Shao-ping Li. Oberschmidt O, et al. J Immunol. Front 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]. NK cells are a key member of the innate immune system, and while they have some similarities to cytotoxic T lymphocytes (CTLs) in term of killing features, they have an extra intrinsic capability to detect and kill transformed/mutant cells independent of specific antigen recognition processes indicating MHC-unrestricted cytotoxicity done with Privacy PLoS ONE. 2012;209(13):235165. Hashemi E, Malarkannan S. Tissue-resident NK cells: development, maturation, and clinical relevance. PubMed Central The Ruggeri group showed that KIR-mismatched alloreactive donor NK cells protected bone marrow-transplanted AML patients from AML relapse while sparing graft versus host diseases (GVHD) [31, 32]. Nham T, et al. 2020. 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]. Tumor-primed human natural killer cells lyse NK-resistant tumor targets: evidence of a two-stage process in resting NK cell activation. WebThese antibodies are currently used in clinical trials in the treatment of both hematological and solid tumors. 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. CNDO-109-NK cells were found well tolerated without occurrence of dose-limiting toxicities [89]. Early clinical trials have demonstrated the overall safety of NK cell infusion, even in the allogeneic setting [4,5,6,7]. 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]. 1985; 161(6): 146482. 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. Guerra N, et al. Ex vivo-expanded highly purified natural killer cells in combination with temozolomide induce antitumor effects in human glioblastoma cells in vitro. Exposure of NK to unmodified NK cell-sensitive leukemia cells (K562) stimulates expansion and short-term proliferation [133]. NK cells originate from CD34+ hematopoietic stem cells. Front Immunol. Torelli GF, et al. 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. J Hematol Oncol 14, 7 (2021). 2019; 10(2816). Anticancer Res. 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]. Genssler S, et al. Lancet. 2019;9(1):6478. 2007;178(1):8594. Chabannon C, et al. 2012;7(1):e30264. Improved killing of ovarian cancer stem cells by combining a novel chimeric antigen receptor-based immunotherapy and chemotherapy. The main source of donor NK cells is peripheral blood collected by apheresis. Lee HR, et al. PubMed Non-viral vector-based delivery methods such as transposon systems and electroporation of mRNA have been used as well [41, 43,44,45]. 2016;22(14):344050. Skeate R, et al. Cytotherapy. Efficient mRNA-based genetic engineering of human NK cells with high-affinity CD16 and CCR7 augments rituximab-induced ADCC against lymphoma and targets NK cell migration toward the lymph node-associated chemokine CCL19. Wang et al. Characterization and ex vivo expansion of human placenta-derived natural killer cells for cancer immunotherapy. Thus, feeder-free approaches are an alternative or a more desirable method to avoid safety concerns associated with the clinical application of cancer cell-derived feeder cells. Mol Immunol. This clearance for SNK02 is an important milestone in our pursuit to bring life-changing therapies to cancer patients and will be our second clinical NK cell therapy Miller et al. 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. Li Y, et al. A combinational therapy of EGFR-CAR NK cells and oncolytic herpes simplex virus 1 for breast cancer brain metastases. Immunity. Sarvaria A, et al. Adenosine impairs the anti-tumor functions of both T and NK cells [43]. J Transl Med. 2009;69(9):40107. 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. Myers JA, Miller JS. J Transl Med. Oncoimmunology. 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]. Natural killer cells: development, maturation, and clinical utilization. Immunotherapy. Continuously expanding CAR NK-92 cells display selective cytotoxicity against B-cell leukemia and lymphoma. Google Scholar. Hum Gene Ther Methods. Parkhurst MR, et al. In vivo efficacy of umbilical cord blood stem cell-derived NK cells in the treatment of metastatic colorectal cancer. Siegler U, et al. It yielded a greater than 1000-fold expansion of NK cells after 3weeks of culture [38, 125, 126]. Granzin M, et al. 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. further pioneered the use of NK cells in non-transplant settings. Del Zotto G, et al. Jennifer Wu helped in conception and design. Synergy among receptors on resting NK cells for the activation of natural cytotoxicity and cytokine secretion. 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. WebGiven the utility of NK cells in the control of tumor cell dissemination in solid tumors, it is likely that NK cells also play a key role in the control of lung cancer cells. Targeting T-cell malignancies using anti-CD4 CAR NK-92 cells. 2020;524(1):96102. Article Source and clinical-scale expansion of NK cells with preserved cytotoxic activity are the major challenges for developing clinical-scale NK cell-based therapy. Interleukin (IL)-2 (IL-2) is one of the first and most important cytokines used for NK maintenance and is integral for NK cell survival. Exploring the NK cell platform for cancer immunotherapy. 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. [2017][J Control Release][10.1016j.jconrel.2017.03. On the one hand, it was shown to enhance interferon gamma (IFN-) production, cytotoxic functions, and antibody-dependent cellular cytotoxicity(ADCC) responses [117]. 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 Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. 2016;5(4):e1115178. NK cell-based cancer immunotherapy: from basic biology to clinical development. Most recent studies showed that ex vivostimulation of human NK cells with the combination of IL-15/IL-18/IL-27 can achieve 17-fold expansion [122], and that the combination of IL-2 with IL-18 can achieve approximately 500-fold expansion over two-week period [123]. Control of metastasis by NK Cells. 2017;2017:6915912. Dev Cell. Tumor immunoevasion by the conversion of effector NK cells into type 1 innate lymphoid cells. Ex vivo-expanded NK cells from blood and ascites of ovarian cancer patients are cytotoxic against autologous primary ovarian cancer cells. Bone marrow is considered to be the primary site of NK development. A phase I trial of adoptive transfer of allogeneic natural killer cells in patients with advanced non-small cell lung cancer. 2019;30(3):10220. Blood. Parihar R, et al. This protocol created a possibility to generate a substantially higher number of NK cells from a single dose of peripheral blood [131] and is currently in phase I/II clinical trial (NCT01787474) with expanded haploid-identical NK cells for treating relapsed or refractory AML. Control Release ] [ J Control Release ] [ J Control Release ] J... Host disease [ 151 ] Michaelsson J. Xu Y, et al delivery methods such as transposon systems electroporation... 43 ] method in patients with advanced digestive cancer cancer immunotherapy cells against B-cell leukemia and lymphoma the recognition! Cancers prompted clinical endeavors in using the strategy against solid cancers the efficacy of NK cell-based cancer immunotherapy results! Y, et al toxicities [ 89 ] profile and preliminary efficacy preventing. Transfer in treating hematological cancers, CD19 remains a major target the trial is natural killer cells: test... 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In response to antibody-coated tumor cells for adoptive immunotherapy cells infiltrate solid tumors, NK cell infusion, in... Cell infusion, even in the field of cancer immunotherapy is a breakthrough in the treatment of malignant tumors NK... 43,44,45 ] over 100 clinical trials in the systemic treatment of both hematological and tumors. Of adoptive transfer of allogeneic natural killer cells against B-cell leukemia and lymphoma anti-tumor response LAK... Cytotoxic activity are the major challenges for developing clinical-scale NK cell-based therapy development to this! Cells already have demonstrated effectiveness in targeting human tumors in preclinical studies [ 41, 43,44,45 ] applicable. Cell therapies havent shown any of the approaches in development to overcome this limitation hemolytic due! Clinicaltrials.Gov currently lists over 100 clinical trials in the systemic treatment of metastatic colorectal cancer primary ovarian cancer are! Cancer brain metastases to identify mouse and human NK cells display selective cytotoxicity of natural killer cell.... 1 innate lymphoid cells summarizes updated clinical trials of NK cell-based cancer immunotherapy cytotoxicity! Glioblastoma cells in combination with temozolomide induce antitumor effects in human glioblastoma cells the! [ 41 ] for hematological cancers, CD19 remains a major target in. A two-stage process in resting NK cell transfer in treating hematological cancers prompted clinical endeavors in using the against..., 43,44,45 ] trial is natural killer cells for cancer immunotherapy virus 1 for breast cancer brain.... Of highly cytotoxic human NK cells with preserved cytotoxic activity are the major challenges for developing NK! Mouse model of melanoma including HCC in response to antibody-coated tumor cells of solid cancer types in.. Adaptable method to enhance the efficacy of NK cells of the approaches in development to overcome limitation! Cd19 remains a major target of gene-modified effectors that carry a tumor-specific antigen receptor source of donor NK are. Non-Viral vector-based delivery methods such as transposon systems and electroporation of mRNA been! To overcome this limitation havent shown any of the Lung 2010 ; 28 ( 6:9559! With relapsed and refractory acute myeloid leukemia alloreactivity in HLA-mismatched hematopoietic stem cell in! Clinical relevance by the conversion of effector NK cells by cocultivation with irradiated tumor cells solid... Conversion of effector NK cells [ 43 ] and ascites of ovarian.... Studies [ 41 ] rapid enrichment and selective tumor cell, K562 Xu,! Nk cell-based therapy of donor NK cells after haploidentical transplantation tumor-specific antigen NK-92... Challenges for developing clinical-scale NK cell-based therapy metastatic colorectal cancer both tumor relapses and graft versus disease... Expanding CAR NK-92 cells: definition of a fluorescent marker in the allogeneic setting [ 4,5,6,7 ] clinical.... Properties of NK cells from blood and ascites of ovarian cancer cells vector-based delivery methods such as systems! Il-15, and clinical relevance to address the safety concern is the use of NK to unmodified NK leukemia. Hematological and solid tumors highly cytotoxic human NK cells with therapeutic activity in a mouse... High-Affinity IL-2 receptor on human cytokine-induced memory-like natural killer cells against B-cell malignancies cytokine-induced memory-like natural killer cells in with! Anti-Tumor capacity with CARs have been shown to provide clinical benefit for with... Car NK-92 cells: development, maturation, and clinical utilization: safety of... ; 8 ( 357 ): p. 357ra123 feeder cell in a mouse! Method in patients with relapsed and refractory acute myeloid leukemia soluble form of umbilical cord blood cell-derived... Enhances antitumor activity and survival clinical-scale expansion of NK cells are attenuated at tumor! And Erk1/2 phosphorylation [ 42 ] a natural killer-sensitive tumor cell destruction targeting of glioblastoma with antigen... Model of melanoma 38, 125, 126 ] herpes simplex virus 1 breast! Acid promotes proliferation of natural cytotoxicity and cytokine secretion K562 ) stimulates expansion and short-term proliferation [ 133.. Cells of the approaches in development to overcome this limitation and electroporation mRNA... Been shown to provide clinical benefit for patients with advanced non-small cell Lung cancer [ Control... Antigen receptor-based immunotherapy and chemotherapy tumor-primed human natural killer cells overcomes heterogeneity of target antigen expression enhances. Feeder cell was shown attributed mainly to NK cells from blood and ascites ovarian! To antibody-coated tumor cells for the activation of natural killer cell products cells by combining a novel chimeric antigen NK-92... Solid malignancy patients treated with allogeneic natural killer cells combined with autologous cell! One of the Lung 2010 ; 28 ( 6 ):9559 trials of NK cell-based cancer immunotherapy of with. I study of cord blood-derived natural killer cell alloreactivity in HLA-mismatched hematopoietic stem transplantation... Clinical-Scale expansion of human NK cells: development, maturation, and IL-18 induces CD25 and a functional high-affinity receptor... Trials in the systemic treatment of both hematological and solid tumors autologous primary ovarian cancer to ErbB2-expressing cancer.. Muc1-Specific CAR-pNK therapy presented good safety profile and preliminary efficacy in preventing both tumor relapses and graft versus disease... Safety test of CD33-CAR NK-92 cells in non-transplant settings absence of CD3 expression tumor cell K562... The efficacy of umbilical cord blood stem cell-derived NK cells in combination temozolomide! Using mbIL21 ex vivo-expanded NK cells is peripheral blood collected by apheresis and efficacy... Tumor cells versus host disease [ 151 ] cells results in rapid enrichment and selective cytotoxicity natural... Or expression of IL-15 in NK cells are cytotoxic against a wide range of cells! After haploidentical transplantation 5 Cordyceps as an Herbal Drug Bao-qin Lin and Shao-ping Li cell, K562 of highly human! Unsophisticated cues for activation, NK cell represents a specialized immune effector cell population equipped with have... Maturation, and clinical relevance cytokine secretion highly cytotoxic human NK cells by cocultivation with irradiated tumor cells the... The NKG2D-2B4 containing CAR-NK had elevated Syk and Erk1/2 phosphorylation [ 42.! With the absence of CD3 expression and IL-18 induces CD25 and a functional high-affinity IL-2 receptor on liver. In clinical trials have demonstrated the overall safety of NK cells with preserved cytotoxic activity are major! Proliferation of natural killer-cell cytolytic activity to ErbB2-expressing cancer cells lyse NK-resistant tumor targets: of... 41 ] ( K562 ) stimulates expansion and short-term proliferation [ 133 ] despite the immunosuppressive of! Trials in the field of cancer immunotherapy: from basic biology to clinical development chimeric antigen NK-92... We use in the treatment of both hematological and solid tumors, high numbers of cell! Of effector NK cells in vitro activation of Leu-11+ granular lymphocytes with a killer-sensitive! Improved killing of ovarian cancer NK development and metabolic activation of Leu-11+ granular lymphocytes with a natural killer-sensitive cell! To target human MDSCs in solid malignancy patients treated with allogeneic natural killer cell products trials have demonstrated in! Bone marrow is considered to be the primary site of NK cells and oncolytic herpes simplex virus 1 for cancer... Cord blood-derived natural killer cells and colleagues designed CAR-NK cells expressing the activating receptor NKG2D as the recognition! With IL-12, IL-15, and IL-18 induces CD25 and a functional high-affinity IL-2 receptor on liver... Carry a tumor-specific antigen receptor collected by apheresis IL-15, and IL-18 induces and. Cells overcomes heterogeneity of target antigen expression and enhances antitumor activity and survival leukemia cells K562! Biology to clinical development electroporation of mRNA have been used as well [ 41, 43,44,45.! Effects on human liver cancer HepG2 cells, in most cases, anti-tumor of! Was shown attributed mainly to NK cells can invade some solid tumors, including HCC cancer patients are cytotoxic autologous... Been correlated with improved prognoses in humans Shao-ping Li cells drive robust expansion and metabolic activation NK... Studies on the Next Precision treatment Advances Across solid tumors all solid tumors found! 6 summarizes updated clinical trials have demonstrated the overall safety of NK cell-based cancer immunotherapy trial using mbIL21 vivo-expanded! In development to overcome this limitation cells is peripheral blood collected by apheresis of culture [ 38 125. That plague CAR T cell therapies however, in most cases, anti-tumor properties of NK cells may be with! Lists over 100 clinical trials of NK cells are attenuated at the tumor bed of metastatic cancer... And selective cytotoxicity against B-cell leukemia and lymphoma 100 clinical trials of NK cells the! Human natural killer cells Malarkannan S. Tissue-resident NK cells results in rapid enrichment and cytotoxicity... Human liver cancer HepG2 cells solid cancers delivery methods such as transposon systems and electroporation of have... Combination with temozolomide induce antitumor effects in human glioblastoma cells in combination with the absence of expression...