scholarly journals Pediatric multicellular tumor spheroid models illustrate a therapeutic potential by combining BH3 mimetics with Natural Killer (NK) cell-based immunotherapy

2022 ◽  
Vol 8 (1) ◽  
Author(s):  
Vinzenz Särchen ◽  
Senthan Shanmugalingam ◽  
Sarah Kehr ◽  
Lisa Marie Reindl ◽  
Victoria Greze ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Tumor Cells ◽  
Pediatric Cancer ◽  
Nk Cell ◽  
Apoptosis Resistance ◽  
Tumor Spheroids ◽  
Multicellular Tumor Spheroid ◽  
Bh3 Mimetics ◽  
Wide Range

AbstractThe induction of apoptosis is a direct way to eliminate tumor cells and improve cancer therapy. Apoptosis is tightly controlled by the balance of pro- and antiapoptotic Bcl-2 proteins. BH3 mimetics neutralize the antiapoptotic function of Bcl-2 proteins and are highly promising compounds inducing apoptosis in several cancer entities including pediatric malignancies. However, the clinical application of BH3 mimetics in solid tumors is impeded by the frequent resistance to single BH3 mimetics and the anticipated toxicity of high concentrations or combination treatments. One potential avenue to increase the potency of BH3 mimetics is the development of immune cell-based therapies to counteract the intrinsic apoptosis resistance of tumor cells and sensitize them to immune attack. Here, we describe spheroid cultures of pediatric cancer cells that can serve as models for drug testing. In these 3D models, we were able to demonstrate that activated allogeneic Natural Killer (NK) cells migrated into tumor spheroids and displayed cytotoxicity against a wide range of pediatric cancer spheroids, highlighting their potential as anti-tumor effector cells. Next, we investigated whether treatment of tumor spheroids with subtoxic concentrations of BH3 mimetics can increase the cytotoxicity of NK cells. Notably, the cytotoxic effects of NK cells were enhanced by the addition of BH3 mimetics. Treatment with either the Bcl-XL inhibitor A1331852 or the Mcl-1 inhibitor S63845 increased the cytotoxicity of NK cells and reduced spheroid size, while the Bcl-2 inhibitor ABT-199 had no effect on NK cell-mediated killing. Taken together, this is the first study to describe the combination of BH3 mimetics targeting Bcl-XL or Mcl-1 with NK cell-based immunotherapy, highlighting the potential of BH3 mimetics in immunotherapy.

scholarly journals DNAM-1 and the TIGIT/PVRIG/TACTILE Axis: Novel Immune Checkpoints for Natural Killer Cell-Based Cancer Immunotherapy

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 877 ◽  
Author(s):  
Beatriz Sanchez-Correa ◽  
Isabel Valhondo ◽  
Fakhri Hassouneh ◽  
Nelson Lopez-Sejas ◽  
Alejandra Pera ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Tumor Cells ◽  
Nk Cell ◽  
Killer Cell ◽  
Cancer Surveillance ◽  
Immune Checkpoints ◽  
Solid Cancer ◽  
Wide Range

Natural killer (NK) cells are lymphocytes of the innate immune response characterized by their role in the destruction of tumor cells. Activation of NK cells depend on a fine balance between activating and inhibitory signals mediated by different receptors. In recent years, a family of paired receptors that interact with ligands of the Nectin/Nectin-like (Necl) family has attracted great interest. Two of these ligands, Necl-5 (usually termed CD155 or PVR) and Nectin-2 (CD112), frequently expressed on different types of tumor cells, are recognized by a group of receptors expressed on T and NK cells that exert opposite functions after interacting with their ligands. These receptors include DNAM-1 (CD226), TIGIT, TACTILE (CD96) and the recently described PVRIG. Whereas activation through DNAM-1 after recognition of CD155 or CD112 enhances NK cell-mediated cytotoxicity against a wide range of tumor cells, TIGIT recognition of these ligands exerts an inhibitory effect on NK cells by diminishing IFN-γ production, as well as NK cell-mediated cytotoxicity. PVRIG has also been identified as an inhibitory receptor that recognizes CD112 but not CD155. However, little is known about the role of TACTILE as modulator of immune responses in humans. TACTILE control of tumor growth and metastases has been reported in murine models, and it has been suggested that it negatively regulates the anti-tumor functions mediated by DNAM-1. In NK cells from patients with solid cancer and leukemia, it has been observed a decreased expression of DNAM-1 that may shift the balance in favor to the inhibitory receptors TIGIT or PVRIG, further contributing to the diminished NK cell-mediated cytotoxic capacity observed in these patients. Analysis of DNAM-1, TIGIT, TACTILE and PVRIG on human NK cells from solid cancer or leukemia patients will clarify the role of these receptors in cancer surveillance. Overall, it can be speculated that in cancer patients the TIGIT/PVRIG pathways are upregulated and represent novel targets for checkpoint blockade immunotherapy.

scholarly journals 799 Neoantigen-cytokine-chemokine multifunctional natural killer cell engager for immunotherapy of solid tumors

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A834-A834
Author(s):  
Xue Yao ◽  
Sandro Matosevic
Keyword(s):  
Tumor Microenvironment ◽  
Cell Therapy ◽  
Nk Cells ◽  
Natural Killer ◽  
Solid Tumors ◽  
Tumor Cells ◽  
Nk Cell ◽  
Killer Cell ◽  
Nk Cell Therapy

BackgroundThe effectiveness of natural killer (NK) cell-based immunotherapy against solid tumors is limited by the lack of specific antigens and the immunosuppressive tumor microenvironment (TME). Glioblastoma multiforme (GBM) is one such heavily immunosuppressive tumor that has been particularly hard to target and remains without a viable treatment. The development of novel approaches to enhance the efficacy of NK cells against GBM is urgently needed. NK cell engagers (NKCE) have been developed to enhance the efficacy of NK cell therapy.MethodsTo improve the clinical efficacy of NK cell therapy, we are developing a new generation of multi-specific killer engagers, which consists of a neoantigen-targeting moiety, together with cytokine and chemokine-producing domains. Neoantigens are new antigens formed specifically in tumor cells due to genome mutations, making them highly specific tools to target tumor cells. Our engager has been designed to target Wilms' tumor-1 (WT-1), a highly specific antigen overexpressed in GBM among other solid tumors. This is done through the generation of an scFv specific targeting the complex of WT-1126-134/HLA-A*02:01 on the surface of GBM. On the NK cell side, the engager is designed to target the activating receptor NKp46. Incorporation of the cytokine IL-15 within the engager supports the maturation, persistence, and expansion of NK cells in vivo while favoring their proliferation and survival in the tumor microenvironment. Additionally, our data indicated that the chemokine CXCL10 plays an important role in the infiltration of NK cells into GBM, however, GBM tumors produce low levels of this chemokine. Incorporation of a CXCL10-producing function into our engager supports intratumoral NK cell trafficking by promoting, through their synthetic production, increased levels of CXCL10 locally in the tumor microenvironment.ResultsCollectively, this has resulted in a novel multifunctional NK cell engager, combining neoantigen-cytokine-chemokine elements fused to an activating domain-specific to NK cells, and we have investigated its ability to support and enhance NK cell-mediated cytotoxicity against solid tumors in vitro and in vivo against patient-derived GBM models. The multi-specific engager shows both high tumor specificity, as well as the ability to overcome NK cell dysfunction encountered in the GBM TME.ConclusionsWe hypothesize that taking advantage of our multi-functional engager, NK cells will exhibit superior ex vivo expansion, infiltration, and antitumor activity in the treatment of GBM and other solid tumors.

Enhancing Natural Killer (NK) Cell Mediated Killing of Non-Hodgkin's Lymphoma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2706-2706 ◽  
Author(s):  
Shivani Srivastava ◽  
Hailin Feng ◽  
Shuhong Zhang ◽  
Jing Liang ◽  
Patrick Squiban ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Tumor Cells ◽  
Mhc Class I ◽  
Median Survival ◽  
Nk Cell ◽  
Normal Donor ◽  
Natural Cytotoxicity ◽  
Raji Cells ◽  
Effector Cells

Abstract Abstract 2706 Poster Board II-682 Follicular lymphoma is incurable with the current chemo- or chemoimmunotherapy with median survival of 8–12 years. Relapse free survival after each subsequent therapy steadily decreases, resulting in an expected median survival of 4.5 years following initial relapse. Hence new treatment strategies are needed. Natural killer (NK) cells are important effector cells in mediating the anti-lymphoma effect of rituximab. Indeed, antibody-dependent cell-mediated cytotoxicity (ADCC) is a major mechanisms of action of rituximab with NK cells being important effector cells. However, in addition to ADCC, NK cells also exert natural cytotoxicity against tumor cells, which is modulated by a balance of inhibitory and activating signals through NK cell receptors. NK cell function is inhibited when their inhibitory killer immunoglobulin-like receptors (KIR) are ligated by their cognate MHC class I antigens on tumor targets. The novel agent IPH2101 (1-7F9) is a fully human monoclonal antibody directed against KIR2DL receptor that blocks the interaction of KIR with its HLA-C ligands breaking NK cell tolerance to autologous tumor cells. We investigated whether the combination of the IPH2101and Rituximab will augment the NK cell mediated cytotoxicity against CD20+ lymphoma targets as compared to rituximab alone. Raji cells are human CD20+ Burkitt lymphoma cell line cells that expresses HLA-A*03,- (ligand to inhibitory KIR3DL2); -B*71[Bw6] (no inhibitory KIR-Ligand) and -Cw*03,w*04 (group 1 and 2 of HLA-C ligands to inhibitory KIR2DL2/3 and KIR2DL1), and were chosen for study because they have HLA-C antigens that ligate the inhibitory KIR2DL2/3 and KIR2DLI receptors, making them a good target to test our hypothesis of inhibiting inhibitory KIR. NK cells were isolated from normal donor PBMC (peripheral blood mononuclear cells) with the Miltenyi NK isolation Kit. Using LDH release based cytotoxicity assay, we show (Figure 1) that the treatment of target Raji cells with Rituximab significantly enhanced natural cytotoxicity of the purified NK cells against Raji cells. IPH2101alone treatment of NK cells also significantly enhanced the cytotoxicity of Raji cells, however, the combination of IPH2101treated NK cells against Rituximab treated Raji cells significantly enhanced cytotoxicity beyond that observed with each agent alone. Effector: Target (E:T) ratios of 14:1 or less, from more than 5 random donors showed similar results indicating a synergistic, or at least and additive effect ( representative experiment shown Figure 1) . In these experiments purified NK cells were treated with 30ug/ml of IPH2101for 30 min and Raji targets were treated with 0.1-30ug/ml of Rituximab for 30 min. NK cells in the presence or absence of IPH2101were co-cultured with Raji cells in the presence or absence of Rituximab for 4 hour in a 96 well plate. NK cytotoxicity was assessed with an LDH release based assay. Our results suggest that there is a positive cooperation between natural cytotoxicity mediated through KIR-MHC blockade and that mediated by ADCC. Indeed, wee have shown that the blockade of KIR-MHC class I interaction by anti-KIR blocking antibody (IPH2101) augments the cytotoxicity of freshly isolated normal donor NK cells against CD20+ lymphoma cell lines as compared to rituximab alone, providing a rationale for the clinical investigation of the combination of IPH2101 (1-7F9) and rituximab in non-Hodgkin's lymphoma Disclosures: Squiban: Innate pharma: Employment.

Pluripotent Stem Cell-Derived Human Natural Killer Cells with Potent Anti-Multiple Myeloma Activity,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4034-4034
Author(s):  
David A. Knorr ◽  
Zhenya Ni ◽  
Allison Bock ◽  
Vijay G. Ramakrishnan ◽  
Shaji Kumar ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Nk Cells ◽  
Natural Killer ◽  
Tumor Cells ◽  
Adoptive Immunotherapy ◽  
Target Cell ◽  
Peripheral Blood ◽  
Nk Cell

Abstract Abstract 4034 Natural Killer (NK) cells are lymphocytes of the innate immune system with anti-viral and anti-cancer activity. Over the past decade, they have gained interest as a promising cellular source for use in adoptive immunotherapy for the treatment of cancer. Most notably, NK cells play an important role in the graft-vs-tumor effect seen in allogeneic hematopoietic stem cell transplantation (allo-HSCT), and a better understanding of NK cell biology has translated into improved transplant outcomes in acute myelogenous leukemia (AML). Small studies have demonstrated a role for NK cell activity in multiple myeloma (MM) patients receiving allo-HSCT. Investigators have also utilized haplo-identical killer immunoglobulin-like receptor (KIR) mismatched NK cells for adoptive immunotherapy in patients with multiple myeloma (MM). Our group has focused on the development of NK cells from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) as a novel starting source of lymphocytes for immunotherapy. We have previously demonstrated potent anti-tumor activity of hESC-derived NK cells in vitro and in vivo against a variety of different targets. We have also shown that iPSC-derived NK cells from a variety of different somatic cell starting sources posses potent anti-tumor and anti-viral activity. Here, we demonstrate hESC- and iPSC-derived NK cell development in a completely defined, feeder-free system that is amenable to clinical scale-up. These cultures contain a pure population of mature NK cells devoid of any T or B cell contamination, which are common adverse bystanders of cellular products isolated and enriched from peripheral blood. Our cultures are homogenous for their expression of CD56 and express high levels of effector molecules known to be important in anti-MM activity, including KIR, CD16, NKG2D, NKp46, NKp44, FasL and TRAIL. We have now tested the activity of hESC- and iPSC-derived NK cells against MM tumor cells in order to provide a universal source of lymphocytes for adoptive immunotherapy in patients with treatment refractory disease. We find that similar to peripheral blood NK cells (PB-NK), hESC- and iPSC-derived NK cells are cytotoxic against 3 distinct MM cell lines in a standard chromium release cytotoxicity assay. Specifically, activated PB-NK cells killed 48.5% of targets at 10 to 1 effector to target ratios, whereas hESC (46.3%) and iPSC (42.4%) derived NK cells also demonstrated significant anti-MM activity. Also, hESC- and iPSC-derived NK cells secrete cytokines (IFNγ and TNFα) and degranulate as demonstrated by CD107a surface expression in response to MM target cell stimulation. When tested against freshly isolated samples from MM patients, hESC- and IPSC-derived NK cells respond at a similar level as activated PB-NK cells, the current source of NK cells used in adoptive immunotherapy trials. These MM targets (both cell lines and primary tumor cells) are known to express defined ligands (MICA/B, DR4/5, ULBP-1, BAT3) for receptors expressed on NK cells as well as a number of undefined ligands for natural cytotoxicity receptors (NCRs) and KIR. As these receptor-ligand interactions drive the anti-MM activity of NK cells, we are currently evaluating expression of each of these molecules on the surface of both the effector and target cell populations. Not only do hESC- and iPSC-derived NK cells provide a unique, homogenous cell population to study these interactions, they also provide a genetically tractable source of lymphocytes for improvement of the graft-vs-myeloma effect and could be tailored on a patient specific basis using banks of hESC-or iPSC-derived NK cells with defined KIR genotypes for use as allogeneic or autologous effector cells. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The PD-1/PD-L1 axis modulates the natural killer cell versus multiple myeloma effect: a therapeutic target for CT-011, a novel monoclonal anti–PD-1 antibody

Blood ◽  
2010 ◽  
Vol 116 (13) ◽  
pp. 2286-2294 ◽  
Author(s):  
Don M. Benson ◽  
Courtney E. Bakan ◽  
Anjali Mishra ◽  
Craig C. Hofmeister ◽  
Yvonne Efebera ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Immune Response ◽  
Nk Cells ◽  
Natural Killer ◽  
Tumor Cells ◽  
Cell Function ◽  
Nk Cell ◽  
Killer Cell ◽  
Cell Immune Response ◽  
Cell Versus

Abstract T-cell expression of programmed death receptor-1 (PD-1) down-regulates the immune response against malignancy by interacting with cognate ligands (eg, PD-L1) on tumor cells; however, little is known regarding PD-1 and natural killer (NK) cells. NK cells exert cytotoxicity against multiple myeloma (MM), an effect enhanced through novel therapies. We show that NK cells from MM patients express PD-1 whereas normal NK cells do not and confirm PD-L1 on primary MM cells. Engagement of PD-1 with PD-L1 should down-modulate the NK-cell versus MM effect. We demonstrate that CT-011, a novel anti–PD-1 antibody, enhances human NK-cell function against autologous, primary MM cells, seemingly through effects on NK-cell trafficking, immune complex formation with MM cells, and cytotoxicity specifically toward PD-L1+ MM tumor cells but not normal cells. We show that lenalidomide down-regulates PD-L1 on primary MM cells and may augment CT-011's enhancement of NK-cell function against MM. We demonstrate a role for the PD-1/PD-L1 signaling axis in the NK-cell immune response against MM and a role for CT-011 in enhancing the NK-cell versus MM effect. A phase 2 clinical trial of CT-011 in combination with lenalidomide for patients with MM should be considered.

Short-term and long-term leptin exposure differentially affect human natural killer cell immune functions

2012 ◽  
Vol 302 (1) ◽  
pp. E108-E116 ◽  
Author(s):  
Christiane D. Wrann ◽  
Tobias Laue ◽  
Lena Hübner ◽  
Susanne Kuhlmann ◽  
Roland Jacobs ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Tumor Cells ◽  
Leptin Receptor ◽  
Nk Cell ◽  
Cell Surface Receptor ◽  
Human Natural Killer Cell ◽  
Immune Functions ◽  
Short Term

Epidemiological studies have indicated that obesity is associated with a higher risk for certain cancers caused by elevated levels of adipocyte-derived hormones. Leptin, one such hormone produced by adipocytes, is a major regulator of metabolism and has also been shown to modulate immunity. However, its role in regulating human natural killer (NK) cell functions is largely unknown. Here, we show that the leptin receptor (Ob-R) is expressed on 5% of NK cells isolated from blood donors, as measured with flow cytometry, and expression of the signal-transducing long form of the leptin receptor Ob-Rb was confirmed with quantitative PCR. The Ob-R+ subpopulation displayed a lower expression of CD16, a cell surface receptor mediating antibody-dependent activation. Short-term stimulation with leptin increased IFNγ secretion, CD69 activation marker expression, and cytotoxic lysis of tumor cells; this was mediated by an improved conjugate forming between NK cells and tumor cells as well as higher expression of tumor necrosis factor-related apoptosis-inducing ligand. On the contrary, long-term incubation with leptin significantly impaired these NK cell immune functions and decreased cell proliferation. In addition, phosphorylation of Jak-2 after leptin stimulation was reduced in peripheral mononuclear blood cells from obese humans compared with normal-weight controls. NK cells represent an immune cell population that is crucial for an effective antitumor response. Here, we show that long-term exposure to leptin, similarly to the situation in obese individuals with elevated serum leptin levels, significantly impairs integral parts of NK cell immune functions, possibly linking leptin to increased cancer susceptibility in obesity.

scholarly journals Overview of Strategies to Improve Therapy against Tumors Using Natural Killer Cell

2020 ◽  
Vol 2020 ◽  
pp. 1-16 ◽  
Author(s):  
Chaopin Yang ◽  
Yue Li ◽  
Yaozhang Yang ◽  
Zhiyi Chen
Keyword(s):  
Immune Function ◽  
Nk Cells ◽  
Natural Killer ◽  
Tumor Cells ◽  
Nk Cell ◽  
Therapeutic Potential ◽  
Tumor Therapy ◽  
Killer Cell ◽  
Oncolytic Viruses ◽  
Target Area

NK cells are lymphocytes with antitumor properties and can directly lyse tumor cells in a non-MHC-restricted manner. However, the tumor microenvironment affects the immune function of NK cells, which leads to immune evasion. This may be related to the pathogenesis of some diseases. Therefore, great efforts have been made to improve the immunotherapy effect of natural killer cells. NK cells from different sources can meet different clinical needs, in order to minimize the inhibition of NK cells and maximize the response potential of NK cells, for example, modification of NK cells can increase the number of NK cells in tumor target area, change the direction of NK cells, and improve their targeting ability to malignant cells. Checkpoint blocking is also a promising strategy for NK cells to kill tumor cells. Combination therapy is another strategy for improving antitumor ability, especially in combination with oncolytic viruses and nanomaterials. In this paper, the mechanisms affecting the activity of NK cells were reviewed, and the therapeutic potential of different basic NK cell strategies in tumor therapy was focused on. The main strategies for improving the immune function of NK cells were described, and some new strategies were proposed.

Fusion Proteins of Ligands for NKG2D and CD20-Directed ScFvs Sensitize Lymphomas for NK Cell-Mediated Lysis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2843-2843
Author(s):  
Christian Kellner ◽  
Daniela Hallack ◽  
Pia Glorius ◽  
Matthias Staudinger ◽  
Sahar Mohseni Nodehi ◽  
...  
Keyword(s):  
T Cells ◽  
B Cell ◽  
Nk Cells ◽  
Natural Killer ◽  
Tumor Cells ◽  
Mhc Class I ◽  
Fusion Proteins ◽  
Nk Cell ◽  
Effector Cells ◽  
Healthy Donors

Abstract Abstract 2843 Natural killer group 2 member D (NKG2D) is an important activating receptor controlling cytotoxicity of natural killer (NK) cells and T cells and plays an important role in immune surveillance against tumors. For redirecting NK cells to B-lymphoid tumor cells two recombinant bifunctional antibody-based fusion proteins were designed in order to coat malignant cells with ligands for NKG2D and attract NK cells. Therefore, a human CD20-directed single-chain fragment variable (scFv) was fused to NKG2D-specific ligands, either MHC class I chain-related protein A (MICA) or unique long 16-binding protein 2 (ULBP2). These two fully human fusion proteins, designated MICA:CD20 and ULBP2:CD20, respectively, were expressed in eukaryotic cells and purified to homogeneity. Size exclusion chromatography revealed that both purified proteins predominantly formed monomers. MICA:CD20 and ULBP2:CD20 specifically and simultaneously bound to CD20 and NKG2D and efficiently mediated lysis of lymphoma cell lines with mononuclear cells from healthy donors as effector cells. Analysis of the activation status of NKG2D-positive T cells and NK cells revealed that MICA:CD20 and ULBP2:CD20 activated resting NK cells, but not T cells, indicating that NK cells were the relevant effector cell population for the two molecules. In cytotoxicity assays using human NK cells from healthy donors, both agents sensitized lymphoma cell lines as well as fresh tumor cells for NK cell-mediated lysis. MICA:CD20 and ULBP2:CD20 induced lysis at low nanomolar concentrations with half maximum effective concentrations between 1 and 4 nM depending on target cells. Interestingly, ULBP2:CD20 exhibited a higher cytolytic potential than MICA:CD20 in terms of maximum lysis. Importantly, MICA:CD20 and ULBP2:CD20 induced lysis of 13/13 tested primary tumor cell samples from patients with different B cell malignancies including chronic lymphocytic leukemia, mantle cell lymphoma and marginal zone lymphoma. Interestingly, cell surface expression of endogenous MICA and ULBP2 was low or not detectable on fresh tumor cells. In addition, ULBP2:CD20 was also capable of inducing lysis of tumor cells in cytotoxicity experiments using autologous patient-derived NK cells as effector cells, indicating that the triggering signal was sufficient to overcome inhibition by interactions between killer cell immunoglobulin-like receptors and MHC class I molecules. Moreover, both MICA:CD20 and ULBP2:CD20 synergistically enhanced antibody-dependent cellular cytotoxicity (ADCC) by the monoclonal antibody daratumumab directed against CD38 which is co-expressed together with CD20 on certain B cell lymphomas. This approach of simultaneously triggering ADCC and natural cytotoxicity by these bifunctional fusion proteins may represent a promising strategy to achieve stronger NK cell-mediated antitumor responses. Disclosures: de Weers: Genmab : Employment. van De Winkel:Genmab: Employment. Parren:Genmab: Employment.

scholarly journals Natural killer cell therapy for hematologic malignancies: successes, challenges, and the future

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Margaret G. Lamb ◽  
Hemalatha G. Rangarajan ◽  
Brian P. Tullius ◽  
Dean A. Lee
Keyword(s):  
Cell Therapy ◽  
Nk Cells ◽  
Natural Killer ◽  
Adoptive Transfer ◽  
Cell Biology ◽  
Nk Cell ◽  
Killer Cell ◽  
Hematologic Malignancies ◽  
Hematopoietic Stem ◽  
Wide Range

AbstractThe adoptive transfer of natural killer (NK) cells is an emerging therapy in the field of immuno-oncology. In the last 3 decades, NK cells have been utilized to harness the anti-tumor immune response in a wide range of malignancies, most notably with early evidence of efficacy in hematologic malignancies. NK cells are dysfunctional in patients with hematologic malignancies, and their number and function are further impaired by chemotherapy, radiation, and immunosuppressants used in initial therapy and hematopoietic stem cell transplantation. Restoring this innate immune deficit may lead to improved therapeutic outcomes. NK cell adoptive transfer has proven to be a safe in these settings, even in the setting of HLA mismatch, and a deeper understanding of NK cell biology and optimized expansion techniques have improved scalability and therapeutic efficacy. Here, we review the use of NK cell therapy in hematologic malignancies and discuss strategies to further improve the efficacy of NK cells against these diseases.

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