2018;51:5561. Clinical evaluation of safety and efficacy of NK cells under this expansion is warranted. A chimeric receptor with NKG2D specificity enhances natural killer cell activation and killing of tumor cells. 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. 2019;9(1):6478. Romee, R., et al. Sustained effector function of IL-12/15/18-preactivated NK cells against established tumors. PubMed You F, et al. 2020;122:2006. Hepatocellular carcinoma (HCC) is a high-incidence malignant tumor worldwide and lacks effective treatment options. Front Immunol. J Immunol. Zhang Q, et al. 1986;137(9):27359. As an alternative to CAR-T cell therapy, CAR-NK cell therapy not only circumvents these challenges but also presents additional major advantages: (i) the ability to use unlimited allogeneic NK source without concern of GVHD [6, 31, 32]; (ii) the potential to generate off-shelf product with NK cell line or iPSC-NK [37,38,39,40,41]; (iii) relatively shortened production time; iv) recognition and killing tumor cells through NK cell native receptors independent of the CAR engineering [42], less likely allowing disease escape through downregulation of the CAR antigens as shown with CAR-T cell therapy [37]. [2017][J Control Release][10.1016j.jconrel.2017.03. 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 Large-scale generation of natural killer lymphocytes for clinical application. 2013;73(6):177786. Granzin M, et al. Article Zeng J, et al. 2017;8(1):67. 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]. Parkhurst MR, et al. 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]. PubMed Central 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. GPC3 is Biol Blood Marrow Transpl. Notably, many tissue-resident NK subsets are now shown to be phenotypically and functionally distinct from conventional peripheral blood NK cells [20]. 2017;47(5):82033. J Immunol Res. WebChimeric antigen receptor T cells therapy (CAR-T therapy) is a class of ACT therapy. 2018;48(6):110417. Jennifer Wu supervised the study. Correction to: IL-27 enhances IL-15/IL-18-mediated activation of human natural killer cells. Moreover, restricted expansion capacity poses a difficulty for improving the efficacy of NK cells through genetic engineering. 2017;92(2):10014. The integration and balance of the activating and inhibitory signals from the ligand/receptor interactions dictates the status of NK cell activation. Typically, the differentiation was induced in embryoid bodies or by OP9 mouse stroma co-culture [111]. Graft-versus-host disease. 2019;10:719. 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. Many efforts are emerging for developing and engineering NK cell-based cancer immunotherapy. 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. 1999;94(1):3339. Miller JS, et al. Mesothelin is a tumor differentiation antigen that is highly overexpressed in several human cancers including malignant mesothelioma, pancreatic, ovarian, and lung adenocarcinoma [91]. Multiple effects of IL-21 on human NK cells in ex vivo expansion. Natural killer (NK) cell is a specialized immune effector cell type that plays a critical role in immune activation against abnormal cells. Cells, 2020; 9(2). There are a number of ongoing clinical trials for cancer immunotherapy using engineered iPSC-NK cells, which are summarized in the following sections. Distribution of reactivity and specificity. 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. Anticancer Res. 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. Control of metastasis by NK Cells. Front Immunol. Source: Liu, S., Galat, V., Galat4, Y. et al. developed an NK cell recruiting protein-conjugated antibody (NRPbody) containing a mesothelin-specific tumor targeting domain Meso-scFv and the chemokine CXCL16 linked by a furin cleavage sites [90]. 2017;8(68):11278396. Specificity and distribution according to genotype. 2012;61(9):145161. Article The advantage of adherent condition is that it provides defined environment for optimizing the differentiation. 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 statement and Ex vivo-expanded natural killer cells demonstrate robust proliferation in vivo in high-risk relapsed multiple myeloma patients. 2012;14(7):83040. WebPhysiological barriers and immunosuppressive microenvironments of solid tumors present considerable hurdles to Chimeric antigen receptor T (CAR-T) cell therapy. 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]. Oncoimmunology. Front Immunol. In the last years, natural killer (NK) cell-based immunotherapy has emerged as a promising therapeutic approach for solid tumors and hematological malignancies. Lee SJ, et al. 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. However, the dose of NK cells being used for therapy is limited. Rosario M, et al. WebCancer immunotherapy has achieved great success in the past few years. Antigens such EGFRvIII, mesothelin, and Her2 have been targeted by CAR-NK cells for the treatment of solid cancers including colorectal cancer, ovarian cancer, breast cancer, and glioblastoma [41, 48]. McMichael EL, et al. Zhang P, et al. J Immunol. Immunobiology. 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. North J, et al. In the last 3 decades, NK cells have been utilized to harness Cancers (Basel), 2020; 12(6). 2019;30(3):10220. WebThis button displays the currently selected search type. 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]. 2015;15:1011. The broad spectrum of human natural killer cell diversity. 2B4 costimulatory domain enhancing cytotoxic ability of anti-CD5 chimeric antigen receptor engineered natural killer cells against T cell malignancies. Mol Ther. WebExperienced R&D leader in pharmaceutical industry focusing on biologics and cell therapy drug discovery for immuno-oncology. CAS PubMed Current preclinical development of NK cell-based therapy was largely inspired by early clinical studies. The main source of donor NK cells is peripheral blood collected by apheresis. Human iPSC-derived natural killer cells engineered with chimeric antigen receptors enhance anti-tumor activity. Front Immunol. Cancer Res. 2010;651:6177. 2014;32(4):102131. Bottcher JP, et al. Guerra N, et al. 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]. 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]. NK cell represents a specialized immune effector cell population equipped with fast-acting and potent anti-tumor capacity. Cell. 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. Additional markers such as lack of c-kit can be used to distinguish human NK (c-kit-) from ILC3s (c-kit+) [14]. Use of CAR-transduced natural killer cells in CD19-positive lymphoid tumors. Ascorbic acid promotes proliferation of natural killer cell populations in culture systems applicable for natural killer cell therapy. Liu E, et al. NK cell-based cancer immunotherapy: from basic biology to clinical development. 2013;3:118. Berraondo P, et al. Wang W, et al. WebThis page lists cancer drugs approved by the Food and Drug Administration (FDA) for the treatment of solid tumors based on their genetic and molecular features and not on Liu E, et al. Lysis of fresh and cultured autologous tumor by human lymphocytes cultured in T-cell growth factor. 2002;100(4):126573. Aiming to generate novel CAR-NK cell-based cancer therapeutics, the consideration of tumor-specific surface antigens and the costimulatory molecules is the The FDA has cleared Artiva Biotherapeutics investigational new drug (IND) application for the chimeric antigen receptor NK (CAR-NK) cell therapy AB-201 for the 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. 2017;19(2):23549. Oncoimmunology. Nat Rev Clin Oncol. 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 Cytokine-mediated activation is frequently employed and currently under extensive investigation. BMC Biotechnol. Knorr DA, et al. The deal gives Merck control of two off-the-shelf solid tumor cell 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 ). Roda JM, et al. Distinctly different from T cell receptors, NK cell receptors are germline-encoded and hard-wired receptors without a requirement for V(D)J recombination. 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. Terms and Conditions, Vallera DA, et al. NKG2D and its ligands in cancer. In treatments of solid tumors, adoptive transfer of ex vivo expanded natural killer (NK) cells has dawned as a new paradigm. An antibody designed to improve adoptive NK-cell therapy inhibits pancreatic cancer progression in a murine model. 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