• NK cell activation and the triggering of effector functions is governed by a complex set of activating and inhibitory receptors. (frontiersin.org)
  • Here, we review tumor-NK cell interactions, discuss the mechanisms by which NK cells generate an antitumor immune response, and discuss NK cell-based therapeutic strategies targeting activating, inhibitory, and co-stimulatory receptors. (frontiersin.org)
  • The activated virus-specific memory CD8+ T cells, expressed the CD94-NK cell receptor subfamily G2a inhibitory molecule. (amparinhibitor.com)
  • BigleyComplexity of interferon- interactions with HSV-the inhibitory CD94-NKG2a molecules, the source of bioactive TGF-1in the latent TG was attributed to CD4+ Foxp3 Treg cells also present within the latent TG (83). (amparinhibitor.com)
  • NK cells express germ-line receptors that are either stimulatory or inhibitory, and the summation of these signals determines activation status ( Caligiuri, 2008 ). (elifesciences.org)
  • Importantly, no major changes in NK cell phenotype, as measured by expression of 15 inhibitory or activating surface receptors, were observed following electroporation with CD16-158V mRNA. (maxcyte.com)
  • The inhibitory effect of T2CA on phopho-galectin-3 expression and the activation of T-cytotoxic and NK cells suggested its protective effects against pathogenic infections and human malignancies via its immune stimulating mechanisms. (arjournals.org)
  • Surface receptors such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1) and nuclear transcription factors attenuate T cell responses, where CTLA-4 competes with CD28 for binding to CD80/86, resulting in inhibitory downstream signalling [ 6 ] . (encyclopedia.pub)
  • These cells secrete immune inhibitory growth factors and cytokines, including vascular endothelial growth factor (VEGF), which is primarily produced by microglia, myeloid-derived suppressor cells (MDSCs) and tumour-associated macrophages (TAMs). (encyclopedia.pub)
  • B46 had no detectable effect on HIV-specific Tcell responses, but this allele is unusual in containing an HLA-C epitope that binds inhibitory receptors on natural killer (NK) cells. (cdc.gov)
  • These cells integrate multiple positive and negative signals through NK cell cytotoxic or inhibitory synapses. (ox.ac.uk)
  • First, γδ T cells exposed to complicated cytokine networks are potentially affected by multiple inhibitory mechanisms. (explorationpub.com)
  • In this manner, the reduced detection of self MHC-I molecules by NK cell-inhibitory receptors coupled with an increase in activating signals by recognition of stress-induced surface ligands promote the cytolytic activity of NK cells. (biomedcentral.com)
  • NK cells recognize the targets through the biased signals transmitted from active or inhibitory receptors. (biomedcentral.com)
  • Tumors escape immune surveillance by inducing various immunosuppressive pathways, including the activation of inhibitory receptors on tumor-infiltrating T cells. (molecule.to)
  • Methods Expanding on Xencor's XmAb bispecific Fc platform, we developed NKE molecules targeting NKG2D, an activating receptor expressed on cytotoxic immune cells, B7H3, a pan tumor antigen, while simultaneously engaging Fc gamma receptors. (bmj.com)
  • In addition, the inherited germline variants from these gene signatures were predominately enriched in T cell function, antigen presentation, and cytokine interactions, likely impairing the adaptive and innate immune response thus favoring a pro-tumorigenic environment. (nature.com)
  • Hurme M, Sihvola M (1984) High expression of the Thy-1 antigen on natural killer cells recently derived from bone marrow. (springer.com)
  • Genetically engineered T cells expressing a chimeric antigen receptor (CAR) are rapidly emerging a promising new treatment for haematological and non-haematological malignancies. (nature.com)
  • Catamaran Bio is developing novel, off-the-shelf chimeric antigen receptor (CAR)-NK cell therapies designed to treat a broad range of cancers, including solid tumors. (pipelinereview.com)
  • Dendritic cells (DCs) are specialized antigen-presenting cells that have a notable role in the initiation and regulation of innate and adaptive immune responses. (mdpi.com)
  • Failed T cell-based immunotherapies in the presence of genomic alterations in antigen presentations pathways may be overcome by NK cell-based immunotherapy. (elifesciences.org)
  • Here, we demonstrate that NK cells (haNKs) engineered to express a PD-L1 chimeric antigen receptor (CAR) haNKs killed a panel of human and murine head and neck cancer cells at low effector-to-target ratios in a PD-L1-dependent fashion. (elifesciences.org)
  • T cell-based immunotherapy, such as immune checkpoint blockade or adoptive T cell transfer, is limited by the ability of T cells to detect major histocompatibility complex (MHC)-presented antigen by tumor cells. (elifesciences.org)
  • Natural killer (NK) cell-based immunotherapy may overcome genetic mechanisms of resistance to T cell-based immunotherapy through antigen- and MHC-independent recognition of malignant cells. (elifesciences.org)
  • Here, we describe the pre-clinical in vitro and in vivo study of irradiated haNK cells engineered to express a second-generation chimeric antigen receptor (CAR) targeting programmed death-ligand 1 (PD-L1). (elifesciences.org)
  • Human leukocyte antigen Cw7 was detected in 4 of 5 recipients, and the fifth case, the antigen was detected in the donor. (ectrx.org)
  • Polyoma BK virus-positive people can be accepted safely for kidney donation, especially with a possible protective role of human leukocyte antigen Cw7. (ectrx.org)
  • Rat natural killer cell antigen, NKR-P1, related to C-type animal lectins is a carbohydrate-binding protein. (bdbiosciences.com)
  • As cells undergo oncogenesis, neoantigens are released and captured on major histocompatibility complex (MHC)/ human leukocyte antigen (HLA) of dendritic cells (DCs) that subsequently mature and migrate to central lymphoid organs. (encyclopedia.pub)
  • Human leukocyte antigen (HLA) alleles have been linked to HIV disease progression and attributed to differences in cytotoxic T lymphocyte (CTL) epitope representation. (cdc.gov)
  • This stress condition can also lead to the attraction of immune cells, notably antigen presenting cells (APCs) (i.e. immature dendritic cells), natural killer cells (NK cells), and cytotoxic T-cells to the site of infection [ 5 , 6 ]. (biomedcentral.com)
  • Virus-based immunostimulatory cytokine and chemokine expression can recruit and activate T cells, antigen-presenting cells (APCs), and natural killer (NK) cells, and subsequently, improve the therapeutic activity of OVs. (biomedcentral.com)
  • Invariant natural killer T (iNKT) cells are CD1d-restricted T cells, which respond rapidly to antigen recognition and promote development of anti-tumor immunity in many tumor models. (biomedcentral.com)
  • While monoclonal antibodies (mAbs) blocking programmed cell death 1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) have been approved for multiple cancer indications, only a subset of patients benefit from immune checkpoint blockade therapies, highlighting the need for additional approaches. (molecule.to)
  • The CXCL9/CXCR3 receptor regulates immune cell migration, differentiation, and activation. (wikipedia.org)
  • Electroporation of primary T cells with Alt-R RNP complex targeted to alpha chain of the T-cell receptor routinely results in over 80% knockout of surface TCR complex, without detectable toxicity ( Figure ). (genengnews.com)
  • Data from a second CAR-NK cell therapy construct engineered using the TAILWIND™ platform are presented in a poster titled "Allogeneic Natural Killer Cells Engineered to Express HER2-directed CAR, Interleukin-15 and TGFβ Dominant Negative Receptor Effectively Control HER2+ Tumors. (pipelinereview.com)
  • One mechanism of NK cell anti-tumor activity is antibody-dependent cellular cytotoxicity (ADCC) induced via Fc receptor (CD16) binding to antibodies. (maxcyte.com)
  • Ex vivo expanded NK cells electroporated with mRNA encoding the high-affinity Fc receptor, CD16-158V, demonstrated a significant increase in CD16 surface expression (Figure 1A). (maxcyte.com)
  • Ex vivo expanded NK cells were electroporated with mRNA (4 µg/10 6 NK cells) encoding the high-affinity, CD16-158V Fc receptor. (maxcyte.com)
  • Recognition of a virus-encoded ligand by a natural killer cell activation receptor. (arjournals.org)
  • Galectin-3 facilitates cell motility in gastric cancer by up-regulating protease-activated receptor-1 (PAR-1) and matrix metalloproteinase-1 (MMP-1). (arjournals.org)
  • Designer T and NK cells are a modality within immunotherapy that manipulates receptor-ligand interactions to enhance cells of the immune system to destroy cancer more effectively. (encyclopedia.pub)
  • Here, the peptide neoantigen on the DCs' MHC is presented to the awaiting CD4 + or CD8 + T cell receptor (TCR) complex. (encyclopedia.pub)
  • Subsequently, binding of the CD28 co-stimulatory receptor to the DCs' CD80/86 receptor fully activates the cytotoxic T cells which then migrate to infiltrate the tumour and kill the cells by locally releasing perforin and granzymes [ 2 ] [ 3 ] . (encyclopedia.pub)
  • PD-1 is an immunoinhibitory receptor that stymies lymphocyte proliferation and cytokine secretion when bound to its membrane-bound or secreted ligands, PD-L1 or PD-L2, expressed by both immune and tumour cells [ 7 ] . (encyclopedia.pub)
  • In addition, activated T cells can express an inducible co-stimulator (iCOS), a surface receptor that is structurally and functionally similar to CD28 and enhances expression of Th2-related interleukin (IL)-10 rather than immune activating IL-2 [ 8 ] . (encyclopedia.pub)
  • The traditional CD8(+)alphabeta T-cell receptor-positive cells are among the best models for the concept of an immunological synapse, in which vectoral signaling is linked to directed secretion in a stable interface to induce apoptotic cell death in an infected cell. (ox.ac.uk)
  • Additionally NKp46 high NK cells expressed elevated levels of the chemokine receptor CXCR3 on mRNA level. (biomedcentral.com)
  • Nevertheless, a recent study from our group with newly developed monoclonal antibodies (mAbs) against the activating receptor NKp46 enabled a more comprehensive insight into the phenotype of porcine NK cells and putative subsets [ 20 ]. (biomedcentral.com)
  • γδ T cells express unique T cell receptor (TCR) γ and TCR δ chains, with structural and functional heterogeneity. (explorationpub.com)
  • Taking advantage of the diverse γδ TCR repertoire or other ligand-receptor interactions, γδ T cells can recognize a broad spectrum of tumor-associated antigens (TAAs) in a major histocompatibility complex (MHC)-independent manner, thereby activating downstream pleiotropic effects. (explorationpub.com)
  • Studies sug- terized by flow cytometry using anti between the immune response and the gest that HCV inhibits receptor genes in CD3, CD56 and CD16 monoclonal virus replication rate [5] and play a cru- the activation of NK cells [20], and the antibodies. (who.int)
  • Cytokines, cancer vaccines, adoptive cell transfers, and especially checkpoint inhibitors constitute valuable elements in the immunotherapeutic armamentarium. (frontiersin.org)
  • However, CD56 dim NK cells can produce cytokines, specifically IFN-γ, after cell triggering via NKp46 of NKp30 activating receptors or after stimulation with combinations of IL-2, IL-12, and IL-15 ( 7 ). (frontiersin.org)
  • Combination of NKEs with proinflammatory cytokines, such as IL15, showed enhancement of the cytotoxic activity against tumor cells and augmented NK cell activation. (bmj.com)
  • Conclusions XmAb bispecific NKEs engineered to engage innate and adaptive immunity show encouraging tumor cell killing activity and synergistic cytotoxicity in combination with proinflammatory cytokines. (bmj.com)
  • Indeed, natural killer (NK) and lymphocyte-activated killer (LAK) cell activation has been demonstrated in vivo and in vitro, and recent genetic studies reveal increased expression of key immune cytokines in response to treatment with PSK. (nih.gov)
  • PSK has also been shown to cause differentiation of leukemic cells in vitro, and this effect has been attributed to induction of differentiation cytokines. (nih.gov)
  • Resveratrol was safe and well tolerated and was associated with significant increases in the numbers of circulating γδ T cells and regulatory T cells and resulted in small, yet significant, decreases in the plasma levels of the proinflammatory cytokines TNF- α and MCP-1 and a significant increase in the plasma antioxidant activity compared with the corresponding antioxidant baseline activity and with that in four control individuals. (hindawi.com)
  • Considering that TGF-1 can induce expression ofIMMUNE Cyclic GMP-AMP Synthase manufacturer response TO HSV-1 Initial host responses to viral infection involve production of interferons-/ by the very first cells infected, IFN- by human natural killer (NK) cells recognizing the gB and gC of virus-infected targets (72), and proinflammatory cytokines and chemokines by monocytic cells (73). (amparinhibitor.com)
  • Besides surgery, radiotherapy and chemotherapy, immune activation by direct application of cytokines, antibodies or adoptive cell therapy are promising approaches. (frontiersin.org)
  • In this study, we addressed feeder cell-free expansion methods using common γ-chain cytokines, especially IL-15 and IL-21. (frontiersin.org)
  • In vivo development and survival of NK cells require cytokines ( 6 - 8 ). (frontiersin.org)
  • In this context, cytokines have been shown to activate NK cells potently during ex vivo expansion ( 9 - 12 ). (frontiersin.org)
  • Cancer immunotherapies can be divided into four major categories: - Cytokines/immunomodulation agents - Monoclonal antibodies - Cell‑based therapies - Oncolytic viruses Though monoclonal antibodies currently represent the largest class of commercialized cancer immunotherapies, cell‑based therapies are rapidly making headway. (technologynetworks.com)
  • Interestingly, cytokines from type-2 innate immune cells, such as M2 macrophages or D2 dendritic cells exhibit a protective effect on both types of diabetes. (biobran.org)
  • Trained immunity of natural killer (NK) cells has shown great potential in the treatment of cancers by eliciting enhanced effector responses to restimulation by cytokines or cancer cells for long time periods after preactivation. (cancerbiomed.org)
  • Functional analyses revealed that splenic NKp46 high NK cells produced much higher levels of Interferon-γ and Tumor Necrosis Factor-α upon stimulation with cytokines or phorbol-12-myristate-13-acetate/Ionomycin compared to the other two subsets. (biomedcentral.com)
  • Besides their role as cytotoxic cells through the production of perforin and granzymes, NK cells are potent producers of cytokines like Interferon (IFN)-γ and Tumor Necrosis Factor (TNF)-α [ 3 ] and thus play important roles in immunomodulation and the defence against viral, parasitic and bacterial pathogens [ 4 ]. (biomedcentral.com)
  • iNKT cells can promote the polarization of adaptive immune responses towards both Th1 and Th2 and can secrete immunosuppressive cytokines [ 19 ]. (biomedcentral.com)
  • During the process of airway inflammation, complex interactions of innate and adaptive immune cells as well as structural cells and their cytokines have many important roles. (cdc.gov)
  • T helper (Th) 2 cells, which recruit and accumulate in the lungs and produce a range of different effector cytokines. (cdc.gov)
  • However, more recent studies have revealed the potential collaboration of other helper T cells and their cytokines in this process. (cdc.gov)
  • The aim of this review is to summarize the current knowledge about the possible roles of newly identified helper T cells derived cytokines (IL-9, 17, 22, 25 and IL-33) in asthma. (cdc.gov)
  • Developed NKEs showed cytotoxic activity and immune cell activation in co-culture studies of human cancer cell lines with either PBMCs, T cells or NK cells. (bmj.com)
  • Immune reactivity occurs through recruitment of immune cells, such as cytotoxic lymphocytes (CTLs), natural killer (NK) cells, NKT cells, and macrophages. (wikipedia.org)
  • First described in 1975, NK cells were initially identified as a distinct sub-population of lymphocytes by their capacity to spontaneously lyse tumor cells ( 1 ). (frontiersin.org)
  • In the context of cancer, appropriately activated DCs can induce anti-tumor immunity by activating innate immune cells and tumor-specific lymphocytes that target cancer cells. (mdpi.com)
  • IL-12 stimulates interferon-γ (IFN-γ) production by natural killer (NK) cells, enhances the cytolytic activities of NK cells and cytotoxic T lymphocytes (CTLs), stimulates the differentiation of Th1 cells and inhibits angiogenesis [ 12 - 14 ]. (biomedcentral.com)
  • In addition to antiviral activity, it activates NATURAL KILLER CELLS and B-LYMPHOCYTES , and down-regulates VASCULAR ENDOTHELIAL GROWTH FACTOR expression through PI-3 KINASE and MAPK KINASES signaling pathways. (lookformedical.com)
  • These CD161 proteins form ~ 60 kDa homodimers that are expressed on natural killer cells and subsets of T lymphocytes, activated monocytes, and dendritic cells. (bdbiosciences.com)
  • These lymphocytes successfully eliminate the genetically unstable tumour cells with intrinsically high immunogenicity [ 4 ] through a series of successive stages [ 5 ] . (encyclopedia.pub)
  • Activated γδ T cells exhibit strong cytotoxic activity and cytokine secretion functions and are effective antitumor lymphocytes with simple and direct recognition modes and rapid responses. (explorationpub.com)
  • The statistically significant rises in the cell count of total lymphocytes, monocytes and natural killer (NK) cells was noteworthy. (iiarjournals.org)
  • Upon the stage of tumorigenesis, down-regulation of the major histocompatibility complex class-I (MHC-I) molecules and also the overexpression of the stress-induced ligands on the surface of malignant cells to avoid recognition by cytotoxic T-lymphocytes (CTLs), make them more sensitive to NK cell-mediated death. (biomedcentral.com)
  • Natural killer T (NKT) cells comprise a subset of lymphocytes originating from a distinct developmental lineage [ 1 ] which bridge innate and adaptive immunity and modulate immune responses in autoimmunity, malignancies and infections [ 2 ]. (biomedcentral.com)
  • Cutaneous T-cell lymphoma (CTCL) (see the image below) is a heterogeneous group of lymphoproliferative disorders characterized by localization of neoplastic T lymphocytes to the skin, with no evidence of extracutaneous disease at the time of diagnosis. (medscape.com)
  • We determined the capacity of the leukemia cell line K562 modified to express a membrane-bound form of interleukin (IL)-15 and 41BB ligand (K562-mb15-41BBL) to generate human NK cells with enhanced cytotoxicity. (aacrjournals.org)
  • Additionally, a 11-year prospective cohort study of Japanese inhabitants linked low peripheral-blood NK cell cytotoxicity with increased cancer risk ( 12 ). (frontiersin.org)
  • Functional activity of NKEs was evaluated via assessing anti-tumor cytotoxicity and activation of NK and T cells in co-culture studies with human cancer cell lines. (bmj.com)
  • V. Enhancement of spontaneous cytotoxicity in patients receiving human leukocyte interferon. (springer.com)
  • Prediction of Chemical Carcinogenicity in Rodents from in Vitro Genetic Toxicity Assays R AYMOND W. TENNANT, BARRY H. MARGOLIN, MICHAEL D. SHELBY, E RROL Z … As an in vivo toxicity endpoint, the acute lung inflammogenicity in a rat instillation model was compared with the in vitro toxicity endpoints comprising cytotoxicity, pro-inflammatory cytokine expression, or haemolytic potential. (holocausto.online)
  • We conduct cytotoxicity estimation using a panel of cell proliferation and viability tests, which can be sorted into four types by different endpoints: Functional assays: assessment of ATP, ADP, ATP/ADP ratios. (holocausto.online)
  • Kroll A(1), Pillukat MH, Hahn D, Schnekenburger J. The in vitro assays covered baseline toxicity in bacteria, oxidative stress, cytotoxicity in mammalian cells and yeast, estrogenicity, and anti-androgenicity. (holocausto.online)
  • In vitro, chemicals such as drugs and pesticides have different cytotoxicity mechanisms such as destruction of cell membranes, prevention of protein synthesis, irreversible binding to receptors etc. (holocausto.online)
  • CD161 molecules are C-type lectin-like receptors that can either activate (CD161a) or inhibit (CD161b) effector leucocyte responses, eg, cytotoxicity or cytokine production, against target cells which express C-type lectin-like related (Clr) molecules. (bdbiosciences.com)
  • Oligosaccharide ligands for NKR-P1 protein activate NK cells and cytotoxicity. (bdbiosciences.com)
  • IgG2a also engages in high affinity interactions with Fc receptors on immune cells which can result in antibody-dependent cell-mediated cytotoxicity (ADCC) as well as antibody-dependent cellular phagocytosis (ADCP) by phagocytosing cells like macrophages 3-8 . (researchsquare.com)
  • Th1 polarization also activates the immune cells in response to IFN-γ. (wikipedia.org)
  • For immune cell activation, CXCL9 stimulate immune cells through Th1 polarization and activation. (wikipedia.org)
  • Immune cells, like Th1, CTLs, NK cells, and NKT cells, show anti-tumor effect against cancer cells through paracrine CXCL9/CXCR3 in tumor models. (wikipedia.org)
  • However, a class of important immune-modulators is conspicuously absent: agents that utilize the power of innate immune cells to eradicate tumors. (frontiersin.org)
  • An important class of innate immune cells that play a critical role in mediating the antitumor immune response is the natural killer (NK) cell. (frontiersin.org)
  • however, little is known about the in vivo effects of this naturally occurring polyphenol on human immune cells. (hindawi.com)
  • We assessed the effects of repeated doses of resveratrol (1000 mg/day for 28 days) on circulating immune cells in healthy Japanese individuals. (hindawi.com)
  • These findings demonstrate that resveratrol has some clear biological effects on human circulating immune cells. (hindawi.com)
  • Thus, the current study evaluated the effects of repeated oral doses of resveratrol on circulating immune cells in healthy individuals. (hindawi.com)
  • Our data revealed that resveratrol induced measurable changes in circulating immune cells in humans and showed considerable antioxidant activities and other biological effects in humans in vivo. (hindawi.com)
  • This class of personalized therapies involves collecting immune cells from an individual, engineering them to recognize and kill cancer cells, before culturing, and reintroducing them into the same individual. (technologynetworks.com)
  • Patient's own immune cells are isolated, genetically modified to improve responses against cancer cells, expanded, and subsequently reintroduced into the individual. (encyclopedia.pub)
  • The rapidly growing tumour alters the balance of interaction between cancer and immune cells, by outstripping its metabolic resources and shifting to glycolysis [ 15 ] . (encyclopedia.pub)
  • While traditionally thought of as innate immune cells, natural killer (NK) cells are now appreciated to have the capacity for long-term adaptation to chemical and viral insults. (ox.ac.uk)
  • Immune cells must be able to adjust their metabolic programs to effectively carry out their effector functions. (biomed.news)
  • This review further emphasizes the diversified cross-talk between γδ T cells and other immune cells. (explorationpub.com)
  • The interactions between tumor and immune cells in the local microenvironment are believed to be involved in the growth, metastasis and invasion of GC [ 2 ]. (biomedcentral.com)
  • Moreover, the complexity of tumor microenvironment (TME), which mainly consists of neoplastic cells, stromal cells, immune cells, soluble factors and extracellular matrix, severely diminishes the efficacy of anti-tumor immunity, thus restraining the effects of various immunotherapies developed during the past decades. (biomedcentral.com)
  • In innate immunity, immune cells are activated by their pattern recognition receptors (PRRs), which bind to pattern molecules of invading pathogens. (fortunejournals.com)
  • The TLRs and CLRs of the immune cells work in coordination with the immune system. (fortunejournals.com)
  • CD226 competes for binding with the same ligands with TIGIT but delivers a positive stimulatory signal to the immune cells. (molecule.to)
  • Programmed cell death-1 (PD-1) shows increased expression on T cells at the tumor site compared to T cells present in the peripheral blood, and anti-PD-1 therapy can inhibit "immune escape" and the immune activation. (wikipedia.org)
  • The non-viral TcBuster™ Transposon System was used to deliver transposons containing a CD70 CAR or CD70 CAR/IL15 expression cassette in primary human peripheral blood NK (PBNK) cells. (pipelinereview.com)
  • PD-L1 CAR haNKs reduced levels of macrophages and other myeloid cells endogenously expressing high PD-L1 in peripheral blood from patients with head and neck cancer. (elifesciences.org)
  • NK cells were isolated from healthy peripheral blood mononuclear cells (CD16-158F/F donors) and expanded ex vivo for 11-15 days with irradiated EBV-SMI-LCL cells. (maxcyte.com)
  • One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells. (lookformedical.com)
  • Experimental treatment approaches include vaccines and nonmyeloablative allogeneic peripheral blood stem cell transplantation. (medscape.com)
  • Other established methods, such as flow cytometry, can then provide extra data regarding immune cell phenotype, activation, and function. (technologynetworks.com)
  • Specifically, demonstrate efficient expression of high-affinity CD16 in NK cells with minimal effects on cell viability and phenotype using mRNA electroporation and assess the effects of CD16-158V expression on rituximab - mediated cytotoxic activity against B cell lymphoma cells. (maxcyte.com)
  • This immunosuppressive helper T cell phenotype can be further induced by the zinc-finger transcription factor GATA3, which regulates Th2 cytokine expression [ 9 ] . (encyclopedia.pub)
  • HLA-B∗46 associates with rapid HIV disease progression in Asian cohorts and prominent differences in NK cell phenotype. (cdc.gov)
  • Phenotypical analyses with newly developed monoclonal antibodies (mAbs) against porcine NKp46 recently revealed that in blood NKp46 - and NKp46 + cells with NK phenotype exist with comparable cytotoxic properties. (biomedcentral.com)
  • In spleen a third NKp46-defined population with NK phenotype was observed that was characterised by a low to negative CD8α and increased NKp46 expression. (biomedcentral.com)
  • In the current study it is shown that this NKp46 high phenotype was correlated with an increased expression of CD16 and CD27 compared to the CD8α + NKp46 - and NKp46 + NK-cell subsets in spleen and blood. (biomedcentral.com)
  • Additionally, a third NK cell population with elevated NKp46 expression levels was identified in high frequencies in spleen and liver, pointing towards a special role of NK cells with this phenotype. (biomedcentral.com)
  • The effects of antibody-mediated blockade of CD1d on DC number and phenotype, priming of anti-tumor T cells, and tumor response to treatment with local radiotherapy and anti-CTLA-4 antibody were evaluated. (biomedcentral.com)
  • The immunosuppressive anthrax lethal toxin impairs NK gamma interferon (IFN-γ) expression, but neither lethal nor edema toxin significantly alters the viability or cytotoxic effector function of NK cells. (utmb.edu)
  • Dendritic cells recognize HSV employing both TLR2 and TLR9 (74). (amparinhibitor.com)
  • Dendritic cells play a key role in processing and presenting antigens to naïve T cells to prime adaptive immunity. (biomed.news)
  • however, the role of circadian rhythms in dendritic cell function is still unclear. (biomed.news)
  • To understand the mechanisms of the immunosuppressive function of iNKT cells, dendritic cells (DCs) were analyzed by immunohistochemistry and flow cytometry in WT and iNKT-deficient (iNKT −/− ) mice. (biomedcentral.com)
  • Given that CD155 is highly expressed by both human and mouse tumors and tumor-infiltrating myeloid cells, it has been proposed that TIGIT might inhibit antitumor immune responses via multiple, sequential steps: first, inhibiting NK cell-mediated tumor cell killing as well as tumor Ag release, then inducing tolerogenic dendritic cells and suppressing CD8+ T cell function via TIGIT+ Tregs, and finally directly inhibiting CD8+ T cell effector functions. (molecule.to)
  • Th1 cells produce IFN-γ, TNF-α, IL-2 and enhance anti-tumor immunity by stimulating CTLs, NK cells and macrophages. (wikipedia.org)
  • To determine a potential role for NK cells in immunity to Bacillus anthracis, we utilized primary human and murine NK cells, in vitro assays, and in vivo NK cell depletion in a murine model of inhalational anthrax. (utmb.edu)
  • NK cell receptors in antiviral immunity. (arjournals.org)
  • However, the human NK cells responsible for the generation and maintenance of trained immunity are largely unknown. (cancerbiomed.org)
  • Protective anti-influenza immunity often correlates with antibody responses to influenza surface glycoproteins, particularly hemagglutinin (HA), the main antigenic determinant on the surface of both influenza virus and infected cells. (researchsquare.com)
  • This sequence of steps may ultimately prevent elimination of cancer cells, so TIGIT is considered to be a key inhibitor in cancer immunity. (molecule.to)
  • In their review " Natural and Adaptive Immunity to Cancer ", Vesely and colleagues draw from recent mouse models of cancer and human clinical data to describe how cells, effector molecules, and pathways of the immune system act to suppress and control tumor cells. (massgenomics.org)
  • We therefore adapted the K562-mb15-41BBL stimulation method to large-scale clinical-grade conditions, generating large numbers of highly cytotoxic NK cells. (aacrjournals.org)
  • The results that we report here provide rationale and practical platform for clinical testing of expanded and activated NK cells for cell therapy of cancer. (aacrjournals.org)
  • There is compelling clinical and experimental evidence to suggest that natural killer (NK) cells play a critical role in the recognition and eradication of tumors. (frontiersin.org)
  • The antitumor effect provided by natural killing has been observed in tumors of hematopoietic and non-hematopoietic origins and reported in diverse in vivo models and clinical series ( 8 ). (frontiersin.org)
  • Using IDT reagents, a team of Stanford University scientists led by Matthew Porteus, M.D., Ph.D., demonstrated robust results in correcting sickle-cell mutations in bone marrow stem cells, potentiating translation into clinical trials. (genengnews.com)
  • Both polysaccharide preparations have documented anticancer activity in vitro, in vivo and in human clinical trials, though PSK has been researched longer and has therefore undergone more thorough laboratory, animal and clinical testing. (nih.gov)
  • Natural killer (NK) cells have innate antibacterial activity that could be targeted for clinical interventions for infectious disease caused by naturally occurring or weaponized bacterial pathogens. (utmb.edu)
  • Our studies demonstrate that NK cells participate in the innate immune response against B. anthracis and suggest that immune modulation to augment NK cell function in early stages of anthrax should be further explored in animal models as a clinical intervention strategy. (utmb.edu)
  • In current clinical development, targeting CD19 + B cell malignancies, which include acute and chronic B-cell leukaemia and B-cell non-Hodgkin lymphomas (NHLs), with anti-CD19 CAR-T cells is one of the most advanced adoptive T-cell therapies and has been approved by the FDA. (nature.com)
  • Our team combines experienced biopharmaceutical leadership with founding scientists who are pioneers in NK cell biology, engineering, manufacturing and clinical application. (pipelinereview.com)
  • The aims of this article are to review the current knowledge regarding therapeutic mechanisms of mesenchymal stem cells in acute liver failure, to discuss recent advancements in preclinical and clinical studies in the treatment of mesenchymal stem cells, and to summarize the methodological improvement of mesenchymal stem cell transplantation in treating liver failure. (springer.com)
  • haNKs represent an 'off the shelf' NK cellular therapy available for pre-clinical and clinical study. (elifesciences.org)
  • Many culturing strategies are based on the addition of feeder or accessory cells, which need to be removed prior to the clinical application of the final NK cell product. (frontiersin.org)
  • Early studies on the transfer of unmodified autologous or allogeneic NK cells have established their clinical safety and demonstrated modest anti-tumor efficacy. (maxcyte.com)
  • Patients homozygous for a natural CD16 polymorphism, CD16-158V which displays higher IgG1 and IgG3 affinity, have improved clinical outcomes upon anti-tumor therapeutic antibody treatment. (maxcyte.com)
  • Only 10% of the human population is homozygous for this polymorphism, suggesting that genetic manipulation of NK cells to express CD16-158V prior to adoptive transfer may improve clinical success not only of NK cell therapies but also anti-tumor IgG1 antibodies. (maxcyte.com)
  • Non-viral engineering of NK cells using MaxCyte ® mRNA electroporation provides significant benefits including high efficiency and low toxicity as well as clinical scalability enabling rapid development of novel adoptive cell therapy approaches. (maxcyte.com)
  • Therefore, toxicity testing is strictly controlled and has to be performed in animals and in GLP (Good Laboratory Practice) conditions to select a safe starting dose for the clinical trial in humans. (holocausto.online)
  • This clinical cancer strategy incorporates advancements in cancer treatment based on a multi-approach to the disease that includes targeting apoptosis, immune cell activation, angiogenesis, restoration of cellular respiration, inhibition of inflammatory mediators, not mentioning some secondary factors such as intoxication, disturbed microbiome, and nervous disorders. (biobran.org)
  • However, the clinical application of tumor-infiltrating γδ T cells has certain limitations. (explorationpub.com)
  • Finally, it retrospectively analyze the activation strategies and clinical relevance of existing γδ T cell adoptive immunotherapies. (explorationpub.com)
  • Thus, restoring the number of NK cells in TME is of great significance for GC clinical treatment. (biomedcentral.com)
  • Recently, anti-TIGIT mAb (tiragolumab) has demonstrated promising clinical efficacy in non-small cell lung cancer treatment when combined with an anti-PD-L1 drug (Tecentriq), leading to phase III trial initiation. (molecule.to)
  • Anti-TIGIT Abs have shown therapeutic effects in several murine cancer models, and there several Abs now under assessment in human clinical trials. (molecule.to)
  • Production of a benchmark anti-human TIGIT mAb currently in a clinical trial 6. (molecule.to)
  • Also, the term "primary cutaneous CD4 + small/medium T-cell lymphoma" was changed to "primary cutaneous CD4 + small/medium T-cell lymphoproliferative disorder" because of its indolent clinical behavior and uncertain malignant potential. (medscape.com)
  • Background Natural Killer cell Engagers (NKEs) are multifunctional molecules that target activating receptors on the surface of NK cells, bind to tumor associated antigens and engage Fc gamma receptors expressed on effector cells of the immune system. (bmj.com)
  • Engagement of NK cells, an effector cell population of the innate immune system, provides an opportunity to target cancers with reduced expression of MHC molecules that are less responsive to therapies targeting the adaptive immune system. (bmj.com)
  • binding of CD94/NKG2a to Qa1 on activated CD4+ T cells provides protection from NK cell-mediated lysis (84).IFN- AND HSV-1 INDUCE EXPRESSION OF SOCS1 SOCS1 expression in response to IFN- by sensory neuronal cells, but not by microglia, is responsible for the lack of expression of class I MHC molecules by sensory neurons (85). (amparinhibitor.com)
  • The CAR-containing exosomes express a high level of cytotoxic molecules and inhibit tumour growth. (nature.com)
  • Traditionally, the in vitro toxicity assays that have been used to identify molecules that carry drug-related DILI risk factors include two-dimensional (2D) cell systems and other standard preclinical model… The principal application of this assay is to rapidly screen test compounds to identify those that induce acute liver cell toxicity. (holocausto.online)
  • After activation, they can directly lyse the targets by generating cytotoxic molecules, such as perforin and granzyme B. Besides, NK cells also secret amounts of immune regulators, especially IFN-γ, to enhance the overall anti-tumor activity [ 5 ]. (biomedcentral.com)
  • This domain interacts with adaptor molecules and activates a cascade which regulates the inflammatory status in cells [12]. (fortunejournals.com)
  • Our proprietary capabilities enable us to harness the natural cancer-fighting properties of NK cells and enhance and tailor their effectiveness with the power of synthetic biology and innovative non-viral cell engineering. (pipelinereview.com)
  • CD3 - CD8α + NKp46 - NK cells show phenotypic and functional properties of NK cells although they produce reduced levels of IFN-γ compared to the NKp46 + subset after in vitro stimulation. (biomedcentral.com)
  • These findings support a role for NK cells in HIV pathogenesis, revealed by the unique properties of the B46 allele common only in Asia. (cdc.gov)
  • CD8+ T cells and macrophages/microglia and their cytokine, TNF-, exert a role in maintaining HSV-1 latency inside the trigeminal ganglia. (amparinhibitor.com)
  • In a preclinical in vivo model of cytokine release syndrome, the administration of CAR exosomes is relatively safe compared with CAR-T therapy. (nature.com)
  • Engineering of IL15 in CAT-179 significantly enhanced NK cell persistence and in vitro and in vivo and eliminated the need for exogenous cytokine support. (pipelinereview.com)
  • The protein encoded by IL-17A is a pro-inflammatory cytokine produced by activated T cells. (cyagen.com)
  • The protein encoded by IL-17A is a proinflammatory cytokine that not only plays a key role in inducing innate immune defense, but also has important effects on host defense, cell transport, immune regulation, and tissue repair. (cyagen.com)
  • This cytokine stimulates non-hematopoietic cells and promotes the production of chemokines, thereby recruiting myeloid cells to the site of inflammation. (cyagen.com)
  • Several chronic inflammatory diseases are associated with high levels of IL-17A cytokine, including rheumatoid arthritis, psoriasis, and multiple sclerosis (MS). Th17 cells and IL-17 are also related with Crohn's disease (CD) and ulcerative colitis (UC), which are two major forms of inflammatory bowel disease (IBD). (cyagen.com)
  • Infusions of natural killer (NK) cells are an emerging tool for cancer immunotherapy. (aacrjournals.org)
  • instead of targeting tumor cells, the goal of immunotherapy is to augment and expand the immune system's intrinsic antitumor response. (frontiersin.org)
  • Thus, addressing the presence of immunosuppressive myeloid cell populations in the periphery and tumor microenvironment of patients with cancer is likely to be required for effective NK cell-based immunotherapy. (elifesciences.org)
  • 4 xCELLigence real-time cell analysis 6 Diverse cancer immunotherapy applications 6 How does the xCELLigence real-time cell analysis assay work? (technologynetworks.com)
  • NK cells play a pivotal role in rapid and highly efficient cancer surveillance and represent a promising avenue for adoptive cell transfer either as a mono- or combination immunotherapy. (maxcyte.com)
  • To determine if the improved response to treatment in the absence of iNKT cells was independent from the immunotherapy employed, 4T1-tumor bearing WT and iNKT −/− mice were treated with local radiotherapy in combination with antibody-mediated CD137 co-stimulation. (biomedcentral.com)
  • A single injection of αβ-interferon (αβ-IFN) (30 000 units/mouse), a major biological modifier of natural killer (NK) cytolytic activity, strongly stimulated NK activity in normal mice, as expected, while the same treatment did not statistically alter the NK response in cyclophosphamide (CY)-suppressed animals. (springer.com)
  • Herberman RB, Nunn ME, Lavrin DH (1975) Natural cytotoxic reactivity of mouse lymphoid cells against syngeneic and allogeneic tumors. (springer.com)
  • Collectively, these preclinical data sets demonstrate the power of Catamaran's fully-integrated TAILWIND™ platform to deliver allogeneic NK cell therapies for solid tumors," said Vipin Suri, PhD, MBA, Chief Scientific Officer of Catamaran Bio. (pipelinereview.com)
  • ABSTRACT Natural kil er (NK) cel s are key players in the immune response to viruses. (who.int)
  • NK cell CD16 expression was measured via flow cytometry for 72 hours post electroporation. (maxcyte.com)
  • We constructed a non-contact co-culturing system and humanized xenograft tumor mice model to detect the influence of GC microenvironment on NK-92 or primary human NK cells viability by flow cytometry. (biomedcentral.com)
  • In vivo studies suggest the axis plays a tumorigenic role by increasing tumor proliferation and metastasis. (wikipedia.org)
  • The autocrine CXCL9/CXCR3 signaling in cancer cells increases cancer cell proliferation, angiogenesis, and metastasis. (wikipedia.org)
  • However, as tumors progress, cancerous cells develop immunosuppressive mechanisms that circumvent NK cell-mediated killing, allowing for tumor escape and proliferation. (frontiersin.org)
  • NKEs promote tumor cell lysis by redirecting NK cells to their targets, and drive activation and proliferation of NK cells. (bmj.com)
  • They confer resistance against many different viruses, inhibit proliferation of normal and malignant cells, impede multiplication of intracellular parasites, enhance macrophage and granulocyte phagocytosis, augment natural killer cell activity, and show several other immunomodulatory functions. (lookformedical.com)
  • The T cells also effectively terminate their activation and proliferation as a means of avoiding autoimmunity, resulting in different phenotypes that either further activate Th1 immune responses or suppress via Th2-driven responses. (encyclopedia.pub)
  • On the other hand, the proliferation of oncolytic viruses into target cells and subsequent recognition of viral elements by pattern recognition receptors (PRRs) such as toll-like receptors can positively affect the development of the innate and adaptive immune responses against tumor cells (Fig. 1 ) [ 6 ]. (biomedcentral.com)
  • In vitro studies based on MCF-7 cell proliferation and induction of vitellogenin in primary culture of rainbow trout hepatocytes. (cdc.gov)
  • Under the method development working group, this project team is developing a manuscript that provides the tools and assays available to assess either cytotoxic T lymphocyte (CTL) or natural killer (NK) cell function. (hesiglobal.org)
  • Moreover, T2CA induced the activation of functional NK cells in human lymphocyte cultures that in turn contributed to the death of K562 leukemic cells in a dose-dependent manner in co-culture experiments. (arjournals.org)
  • Engineered cells were highly cytotoxic against multiple CD70-positive tumor cells lines derived from renal cell carcinoma (RCC) and acute myeloid leukemia (AML). (pipelinereview.com)
  • The development of clinically applicable methods to produce large numbers of fully functional NK cells is a critical step to maximize the potential of this approach. (aacrjournals.org)
  • The defining functional feature of NK cells remains their intrinsic ability to conduct "natural killing" of cellular targets without prior sensitization. (frontiersin.org)
  • We have now shown preclinical efficacy in multiple xenograft models with two differentiated CAR-NK cell therapies engineered with the functional attributes necessary for durable efficacy in solid tumors and manufactured using an efficient non-viral cell engineering system. (pipelinereview.com)
  • A main challenge of NK cell therapy is that it requires a high amount of functional NK cells. (frontiersin.org)
  • Inohara H, Raz A. Functional Evidence That Cell-Surface Galectin-3 mediates homotypic cell-adhesion. (arjournals.org)
  • Therefore, in this study we focused on functional and phenotypical properties of CD8α dim/- NKp46 high NK-cells in the spleen. (biomedcentral.com)
  • At present, the phenotypic heterogeneity and functional variation of human γδ T cells are increasing. (explorationpub.com)
  • Experimental data in different systems indicate a functional plasticity of iNKT cells. (biomedcentral.com)
  • A considerable number of phenotypically and functionally different NK-cell subsets have been identified up to date [ 5 ]. (biomedcentral.com)
  • In the mouse likewise CD27 and CD11b (Mac-1) are used to dissect NK cells into functionally and developmentally different subsets [ 9 ]. (biomedcentral.com)
  • Despite these hints on important functions of porcine NK cells in vivo, so far no investigations on the existence of functionally differing NK-cell subsets have been reported. (biomedcentral.com)
  • In contrast, NKp46 in the pig was shown to divide porcine CD3 - CD8α + NK cells into NKp46 - and NKp46 + subsets in blood and all organs tested [ 20 ]. (biomedcentral.com)
  • It is of great significance to gain insight into the classification of γδ T cell subsets. (explorationpub.com)
  • Our results confirm a potential role of NK cells and the different subsets in the pathogenesis of chronic HCV infection. (who.int)
  • Hepatitis C virus (HCV) infection has impaired cellular immune response and circulating NK cells, NK subsets (in- the ability to establish chronic infection virus persistence [8]. (who.int)
  • The expanded NK cells were significantly more potent than unstimulated or IL-2-stimulated NK cells against acute myeloid leukemia cells in vitro . (aacrjournals.org)
  • TGFBIp significantly increased platelet transmigration and we demonstrate TGFBIp deposits in the wall of human arteries. (bvsalud.org)
  • In in vitro studies, resveratrol significantly improved the growth of γδ T cells and regulatory T cells. (hindawi.com)
  • The in vivo depletion of murine NK cells does not alter animal survival following intranasal infection with B. anthracis spores in our studies but significantly increases the bacterial load in the blood of infected animals. (utmb.edu)
  • The T2CA activated T-cytotoxic and NK cells significantly contributing to its immune stimulating effect. (arjournals.org)
  • Curiously, during CMC assays, nkl transcription was significantly increased in seabream HKLs against NNV-infected fish cell lines but this was not observed in sea bass leucocytes. (360qikan.com)
  • In the first weeks of treatment at least, the raised cell count of NK cells correlated with the significantly increased cytotoxic activity versus tumor cells ex vivo. (iiarjournals.org)
  • CD1d blockade restored the number of DC in WT mice, improved T cell priming in draining lymph nodes and significantly enhanced response to treatment. (biomedcentral.com)
  • The percentage of CD56(bright) cells was significantly higher than the control group ( P = 0.04). (who.int)
  • The frequency of CD3+CD56- T cells was significantly lower in both the chronic and resolved groups compared to the control group ( P = 0.04). (who.int)
  • clarified that CXCR3 deficient mice displayed increased IL-4 production and M2 polarization in a murine breast cancer model, and decreased innate and immune cell-mediated anti-tumor responses. (wikipedia.org)
  • Thymosin α 1 was, moreover, able to accelerate the recovery rate of NK activity in bone marrow reconstituted murine chimeras. (springer.com)
  • Compared to human NK cells, murine NK cells have a similar, though less potent, activity against intracellular and extracellular B. anthracis. (utmb.edu)
  • Deletion of galectin-3 in the host attenuates metastasis of murine melanoma by modulating tumor adhesion and NK cell activity. (arjournals.org)
  • Scientific Methods: In vitro growth inhibition assays were completed with AHCC alone and in combination with PLD in panel of human cancer cell lines and findings confirmed in vivo in an ovarian cancer xenograft mouse model. (researchgate.net)
  • The functionality of the IL-12 or CD gene products expressed from these vectors was validated by splenic interferon (IFN)-γ production or viability assays in cultured cells. (biomedcentral.com)
  • While the data provided by these assays help piece together an understanding of different facets of immune cell‑mediated killing, it is important to note that the parameters being reported often do not correlate with target cell killing efficacy in vivo. (technologynetworks.com)
  • In vitro toxicity assays are used to determine the potential of a new pharmaceutical, agrochemical, food additive, or other chemical product to be hazardous to humans.In vitro studies, which are performed on cultured bacterial or mammalian cells, can be used as an initial screen to avoid the unnecessary use of animals in determining which candidates should move forward for further safety testing. (holocausto.online)
  • Extraction and direct contact assays were performed using human epidermal keratinocytes and mouse fibroblasts and mouse epithelial cells. (holocausto.online)
  • Administration of QIV with the two adjuvants, individually or combined, resulted in enhanced HA-specific serum ELISA IgG titers, serum hemagglutination inhibition (HAI) titers and splenic T cell responses as examined by IFN-γ and IL-4 enzyme-linked immunosorbent spot (ELISPOT) assays, 4-weeks post-prime and post-boost vaccination in BALB/c mice. (researchsquare.com)
  • In the last years, adoptive transfer of natural killer (NK) cells came into the focus of translational medicine, because of their high cytotoxic potential against transformed malignant cells. (frontiersin.org)
  • With their ability to detect and directly destroy virally infected or malignant cells, natural killer (NK) cells form an important part of the first line defense of the immune system. (frontiersin.org)
  • Malignant transformation of thyroid follicular cells by galectin-3. (arjournals.org)
  • Compared with conventional cancer treatments, the main advantage of oncolytic virotherapy is its tumor-selective replication followed by the destruction of malignant cells without damaging healthy cells. (biomedcentral.com)
  • The recent FDA approvals of the programmed cell death protein 1 (PD-1)-targeted checkpoint inhibitors pembrolizumab and nivolumab mark the latest successes in the rapidly expanding field of cancer immunotherapies. (frontiersin.org)
  • Therefore, NKEs have a potential to provide an additional treatment option to patients who respond poorly to T cell tailored immunotherapies. (bmj.com)
  • This ammonia clearance machinery might be targeted to improve T cell-based cancer immunotherapies. (biomed.news)
  • According to current challenges, there is a need to explore innovative immunotherapies, maximize the tumor-killing efficacy of γδ T cells, and attenuate or eliminate tumor immunosuppression. (explorationpub.com)
  • These results have important implications for the design of immunotherapies targeting iNKT cells. (biomedcentral.com)
  • Despite their efficiency, adoptive T-cell therapies show unique toxicities, which are distinct from those seen with conventional chemotherapies, monoclonal antibodies (mAbs), and small-molecule-targeted therapies. (nature.com)
  • Establish overexpression of high-affinity CD16 on NK cells as a potential combination therapy for improving ADCC activity of anti-tumor monoclonal antibodies. (maxcyte.com)
  • We seek to de-risk humanized anti-TIGIT antibodies through in vivo studies with Biocytogen's transgenic mouse lines. (molecule.to)
  • Herberman RB, Ortaldo JR, Mantovani A, Hobbs DS, Kung HF, Pestka S (1982) Effect of human recobinant interferon on cytotoxic activity of natural killer (NK) cells and monocytes. (springer.com)
  • Our results demonstrate potent antibacterial activity by human NK cells against B. anthracis bacilli within infected autologous monocytes. (utmb.edu)
  • When the Qa1b /CD94-NKG2a interaction was blocked in ex vivo experiments, neuronal lysis occurred. (amparinhibitor.com)
  • Engineered NK cells had an enhanced ability to mediate ADCC as measured both via NK cell degranulation (CD107a expression, Figure 2A) and specific lysis of B cell lymphoma cells ( 51 Cr release assay, Figure 2B). (maxcyte.com)
  • Oncolytic viruses (OVs) specifically induce cancer cells death by infection of and spreading on tumor cells through different mechanisms such as direct lysis effect or adjacent cells fusion. (biomedcentral.com)
  • We found L-KYN, mainly generated through indoleamine 2, 3-dioxygenase (IDO) from GC cells, impaired NK cells viability in TME. (biomedcentral.com)
  • This action of PSK may play a role in preventing second primary tumors when an inducing agent, such as tobacco or asbestos, is suspected and may also prevent second malignancies due to the carcinogenic effects of radiotherapy and cytotoxic chemotherapy. (nih.gov)
  • These results demonstrate that NK cells engineered via the TAILWIND™ platform have a favorable pharmacologic profile and the potential for treatment of solid tumors. (pipelinereview.com)
  • We have evaluated the antitumor effect of combining IL-12 with CD gene transfer in mice bearing renal cell carcinoma (Renca) tumors. (biomedcentral.com)
  • Treatment of syngeneic tumors resulted in CD8 and PD-L1-dependent tumor rejection or growth inhibition and a reduction in myeloid cells endogenously expressing high levels of PD-L1. (elifesciences.org)
  • Special advances are achieved in HER-positive tumors using targeted therapy with drugs which suppress the tumor cell growth factors (trastuzumab, herceptin). (cttjournal.com)
  • Natural killer (NK) cells are an integral component of the innate immune system, which undertake the immune surveillance against tumors [ 5 ]. (biomedcentral.com)
  • There are mounting evidence suggesting that the improvement of NK infiltration or function in tumors is obviously beneficial for patient survival [ 6 ]. (biomedcentral.com)
  • The complexity of the human bone marrow, with context to haematological malignancies, is more difficult to elucidate with the present strategies compared to the niche of solid tumors. (fortunejournals.com)
  • Relevant information has now been established on solid tumors and their micro-environments, which include immune, endothelial and mesenchymal cells. (fortunejournals.com)
  • Here we describe a novel mechanism of tumor immune escape mediated by iNKT cells that limit priming of anti-tumor T cells by controlling DC in tumors and draining lymph nodes. (biomedcentral.com)
  • Increasingly, renal cell cancers are diagnosed at an earlier stage, and nephron-sparing surgery and thermal ablation are gaining acceptance as a treatment of choice for smaller tumors. (medscape.com)
  • CXCL9 has also been identified as candidate biomarker of adoptive T cell transfer therapy in metastatic melanoma. (wikipedia.org)
  • Therapeutic intervention aims to reverse tumor-induced NK cell suppression and sustain NK cells' tumorlytic capacities. (frontiersin.org)
  • However, the therapeutic outcome appears not to be high as expected, presumably because the in vivo gene delivery efficiency is low. (biomedcentral.com)
  • New therapeutic concepts in anti-tumor therapy aim to modulate the patient's immune system to increase its aggressiveness or targeted effects toward tumor cells. (frontiersin.org)
  • In a proof of concept in vivo study, we also observed a therapeutic effect of adoptively transferred IL-15 expanded and IL-21 boosted NK cells in combination with image guided high precision radiation therapy using a luciferase-transduced RMS xenograft model. (frontiersin.org)
  • While increased CD16 expression was transient in nature, this may not negatively impact the therapeutic potential of engineered NK cells due to the short persistence of adoptively transferred NK cells. (maxcyte.com)
  • This review provides an overview of work on cytotoxic immunological synapses and suggests pathways forward in applying this information to the development of therapeutic agents. (ox.ac.uk)
  • Human sodium/iodide symporter (hNIS) is considered as one of the most prevalent nuclear imaging reporter transgenes that provides precise information regarding the kinetics of gene expression, viral biodistribution, toxicity, and therapeutic outcomes using the accumulation of radiotracers at the site of transgene expression. (biomedcentral.com)
  • Based on this, we generated GPX4 over-expressed NK-92 cells, and found these cells showed therapeutic potential towards GC. (biomedcentral.com)
  • CAT-179 showed potent anti-tumor activity in vivo against a xenografted HER2+ N87 gastric cancer cell line and led to a significant survival benefit in tumor-bearing mice. (pipelinereview.com)
  • of various populations of NKR+ T cells whole blood were withdrawn from Natural killer (NK) cells are potent have been reported to be impaired in each participant on ethylenediamine- antiviral cells which eliminate the vi- chronic hepatitis C patients [16,21]. (who.int)
  • These data have identified several promising candidate NKEs for future in vivo efficacy studies in mouse tumor models expressing B7H3. (bmj.com)
  • CAMBRIDGE, MA, USA I November 10, 2022 I Catamaran Bio , Inc., a biotechnology company developing off-the-shelf NK cell therapies to treat cancer, today announced new data demonstrating preclinical efficacy of two CAR-NK cell therapies in solid and hematological cancers. (pipelinereview.com)
  • While many methods have been developed to screen and evaluate the efficacy of immune cell‑mediated killing, there is a need for a more robust in vitro assay to accurately predict the in vivo behavior of therapies. (technologynetworks.com)
  • Preclinical studies have shown that resveratrol induces immunomodulatory effects, including the upregulation of NKG2D receptors on natural killer cells (NK) that it promotes the NKG2D-dependent killing of tumor cells [ 13 , 14 ] and the induction of regulatory T cells (Treg) in the colonic tissues of mice exposed to colonic inflammatory stress [ 15 ]. (hindawi.com)
  • We investigated the possibility of thymosin α 1 cooperating with αβ-IFN in boosting NK activity in CY-suppressed animals. (springer.com)
  • The results show that treatment with thymosin α 1 (200 μg/kg) for 4 days, followed by a single injection of αβ-IFN 24 h before testing, strongly restored NK activity in CY-suppressed mice. (springer.com)
  • Bardos P, Bach JF (1982) Modulation of mouse natural killer cell activity by serum thymic factor. (springer.com)
  • Augmentation of mouse natural killer cell activity by interferon and interferon inducers. (springer.com)
  • Gidlund M, Orn A, Wigzell H, Senik A, Gresser I (1978) Enhanced NK cell activity in mice injected with intereron and interferon inducers. (springer.com)
  • Kaiserlian D, Bardos P, Bach JF (1983) In vitro modulation of mouse natural killer (NK) cell activity by the serum thymic factor (FTS). (springer.com)
  • Maluish AE, Ortaldo JR, Herberman RB (1982) Modulation of NK activity by recombinant leucocyte interferon in advanced cancer patients. (springer.com)
  • Surprisingly, NK cells also mediate moderate antibacterial effects on extracellular vegetative bacilli but do not have activity against extracellular or intracellular spores. (utmb.edu)
  • The antitumor effects were then evaluated by measuring tumor regression, mean animal survival time, splenic natural killer (NK) cell activity and IFN-γ production. (biomedcentral.com)
  • The combined gene transfer increased splenic NK cell activity and IFN-γ production by splenocytes. (biomedcentral.com)
  • Hence, we established a two-phase expansion protocol with IL-15 to induce an early NK cell expansion, followed by short exposure to IL-21 that boosted the cytotoxic activity of NK cells against RMS cells. (frontiersin.org)
  • In vitro cytotoxic activity against rituximab-coated CD20+ B cell lymphoma cells of CD16-engineered or non-engineered NK cells was assessed 24 hours post electroporation. (maxcyte.com)
  • An MTT assay was used to determine cell metabolic activity and a TUNEL assay for detecting DNA fragmentation. (holocausto.online)
  • It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. (lookformedical.com)
  • T2CA inhibited the expression of phosphorylated galectin-3 expression in human glioblastoma cell line which in turn inhibits the activity of MMP2 and MMP9 proteins in zymography investigations and inhibits migration of cancer cells in in vitro scratch assay. (arjournals.org)
  • The NK factor (product of NK cells and ex vivo activity) was determined to assess the total NK activity more accurately, which rose up to 50% compared to the baseline value. (iiarjournals.org)
  • 1999. Transactivation activity of human, zebrafish, and rainbow trout aryl hydrocarbon receptors expressed in COS-7 cells: Greater insight into species differences in toxic potency of polychlorinated dibenzo- p -dioxin, dibenzofuran, and biphenyl congeners. (cdc.gov)
  • NK cells are now accepted to play an important role in both the adaptive and innate immune responses that govern infection, autoimmunity, and tumor immunosurveillance ( 2 , 3 ). (frontiersin.org)
  • Patrolling leukocytes detect mutated, early transformed cells, deem them sufficiently "non-self" and co-ordinately eliminate them, as predicted by the cancer immunosurveillance concept [ 1 ] . (encyclopedia.pub)
  • Immunosurveillance , in which transformed cells are identified and destroyed before they can establish malignancy. (massgenomics.org)
  • Therefore porcine splenic NKp46 high NK cells represent a highly activated subset of NK cells and may play a profound role in the immune surveillance of this organ. (biomedcentral.com)
  • For immune cell differentiation, some reports show that CXCL9 lead to Th1 polarization through CXCR3. (wikipedia.org)
  • Taken together the data support the concept that the synergic effect between thymosin α 1 and αβ-IFN could be the result of effects on differentiation of the NK lineage at different levels. (springer.com)
  • Moreover, CAR-T cells are vulnerable to immunosuppressive mechanisms. (nature.com)
  • Previous studies have proven that rodent and human MSCs can differentiate into HLCs in vitro and in vivo , which is one of the mechanisms of MSCs in the treatment of liver failure. (springer.com)
  • Cells already have an array of intrinsic defense mechanisms that halt the transformation process. (massgenomics.org)
  • A single dose of engineered NK cells expressing CD70 CAR and secreted IL15 reduced tumor burden and increased survival in an RCC xenograft model, without the need for exogenous IL15. (pipelinereview.com)
  • Western blot hybridization studies showed that T2CA downregulates the expression of total gal 3 proteins and extended the survival of AKR/J mice injected with Ehrlich ascites tumor cells in the Kepler-Meier survival curve analysis. (arjournals.org)
  • Amino acid metabolism is essential for cell survival, while the byproduct ammonia is toxic and can injure cellular longevity. (biomed.news)
  • A multivariate Cox analysis was performed to show that the intra-tumoral NK cell density was positively related with the overall and disease-free survival of GC patients [ 9 ]. (biomedcentral.com)
  • Here, we show greater T cell responses when mice are immunised in the middle of their rest versus their active phase. (biomed.news)
  • Inspired by the accidental discoveries, we constructed a NK-92 cell strain with high expression of GPX4 and treated the humanized xenograft tumor mice model with the NK-92 cells. (biomedcentral.com)
  • Surprisingly, we previously found that mice deficient in iNKT cells developed spontaneous CD8 + T cells responses partially effective at inhibiting metastases in mice bearing the 4T1 mammary carcinoma, and showed a markedly improved response to treatment with local radiotherapy and anti-CTLA-4 antibody compared to wild type (WT) mice. (biomedcentral.com)
  • Consistently, priming of T cells to a tumor-specific CD8 T cell epitope in mice treated with radiotherapy and anti-CTLA-4 or anti-CD137 was markedly enhanced in iNKT −/− compared to WT mice. (biomedcentral.com)
  • Human NK cells are phenotypically characterized by the expression of CD56 and the absence of CD3 and can be further subdivided into a CD56 bright population and a CD56 dim population. (frontiersin.org)
  • While the percentages of CD56 (dim) cells and their CD16 expression were lower in the chronic group, this was not statistically significant. (who.int)
  • The elimination or persistence (NKRs) and mediate functions of both cells and CD56+NT cells was charac- of the infection depends on a balance T cells and NK cells [13]. (who.int)
  • 1,3,4 Such activation is determined by the detection of free viral particles in the urine by polymerase chain reaction (PCR), intranuclear viral-inclusion-bearing cells, decoy cells in urine cytology samples, and viremia by plasma PCR. (ectrx.org)
  • Recently, altered NK cell frequency polymerase chain reaction (Stratagene has been suggested to contribute to the Mx3000P). (who.int)
  • Nascent transformed cells elicit NK cell activation and are eliminated. (frontiersin.org)
  • Typically, CARs consist of a target binding domain, which is an extracellular domain that is specifically expressed by CAR-T cells, a transmembrane domain, and a signalling domain, which is an intracellular domain that provides an activation signal to T cells. (nature.com)
  • However, direct injection of IL-2 has been shown to be accompanied by severe side effects, such as vascular leak syndrome, activation-induced cell death, and strong induction of regulatory CD4 pos T cells, which did not occur after IL-15 administration ( 15 , 16 ). (frontiersin.org)
  • Unbiased transcriptomic screens showed increased NK cell activation in people with HIV, without B46, and simultaneous single-cell profiling of surface proteins and transcriptomes revealed a NK cell subset primed for increased responses in the absence of B46. (cdc.gov)
  • This type of hyperinflammatory state is reminiscent of 2 rheumatologic disorders known as macrophage activation syndrome and hemophagocytic lymphohistiocytosis, which are characterized by macrophage and T-cell activation. (cdc.gov)
  • An evaluation of 2 cohorts of patients with EVD revealed that a marker of macrophage activation (sCD163) but not T-cell activation (sCD25) was associated with severe and fatal EVD. (cdc.gov)
  • CAT-179 was resistant to TGFβ-mediated immunosuppression in vitro , indicating that the cells will be protected from TGFβ-mediated immune suppression in the tumor microenvironment. (pipelinereview.com)
  • γδ T cells recruited into the tumor microenvironment can act as effector cells to mediate cancer immune surveillance. (explorationpub.com)
  • Therefore, an in-depth understanding of γδ T cells that play conflicting roles in the tumor microenvironment is necessary. (explorationpub.com)
  • These results demonstrate the potential for targeting CD70 with CAR-NK cell therapy for the treatment of AML, RCC, and other CD70-positive malignancies while overcoming fratricide issues by engineering with a non-viral transposon delivery system in combination with CRISPR/Cas9 editing. (pipelinereview.com)
  • Natural killer (NK) cells can kill cancer cells in the absence of prior stimulation and hold considerable potential for cell-based therapies targeting human malignancies ( 1 - 4 ). (aacrjournals.org)
  • Two distinct pathways mediate this process, both of which are facilitated by a cytotoxic immunological synapse. (ox.ac.uk)
  • In the early phases of cancer immune surveillance, NK cells directly identify and lyse cancer cells. (frontiersin.org)
  • NK cell infiltration into tumor tissue is associated with better disease prognosis in colorectal cancer, clear cell renal cell carcinoma, and lung carcinomas ( 9 - 11 ). (frontiersin.org)
  • Industrial Relevance: This study presents an example of the successful integration of a well- known herbal supplement, AHCC, with traditional western medicine cytotoxic agent, pegylated liposomal doxorubicin, for the treatment of recurrent ovarian cancer. (researchgate.net)
  • These finding are particularly beneficial in the treatment of recurrent cancer when maintaining a good quality of life during chemotherapy is a priority and allows patients to have a natural, nutritional approach to preventing and managing chemotherapy adverse effects. (researchgate.net)
  • Resveratrol is the most extensively studied stilbene, and preclinical studies have revealed that this compound has several biological effects including, antioxidant, anti-inflammatory, and cytotoxic effects against human cancer cell lines derived from various tumor types [ 1 , 3 , 4 ]. (hindawi.com)
  • A single normal cell randomly acquires a series of mutations that allows it to proliferate and to be transformed into a cancer cell (i.e., founding clone), which initiates tumor progression and recurrence. (nature.com)
  • Bash JA, Woody JN, Neefe JR (1982) Phase I trial of immunomodulatory activities of human leukocyte interferon in advanced cancer patients. (springer.com)
  • Cancer cells also recruit and alter nearby stromal cells to aid the tumour cells in avoiding immune detection and destruction [ 16 ] [ 17 ] . (encyclopedia.pub)
  • During the last ten years or so, she has developed a particular interest in researching cancer as a process, focusing on its early detection and the ways in which nutritional, plant-derived and other natural substances can be used to help restore homoeostasis, cellular chemistry and health. (thecancerrevolution.co.uk)
  • In cancer contexts, TIGIT is known to be upregulated in tumor-infiltrated T cells. (molecule.to)
  • Renal cell carcinoma (see the image below) is the most common type of kidney cancer in adults. (medscape.com)
  • Compared with CAR-T cells, CAR exosomes do not express Programmed cell Death protein 1 (PD1), and their antitumour effect cannot be weakened by recombinant PD-L1 treatment. (nature.com)
  • PHOSPHORYLATION of IRF-3 causes the protein to be translocated from the CYTOPLASM to CELL NUCLEUS where it binds DNA , and activates transcription. (lookformedical.com)
  • Yamaoka K, Ohno S, Kawasaki H, Suzuki K. Overexpression of a beta-galactoside binding protein causes transformation of BALB3T3 fibroblast cells. (arjournals.org)
  • The most commonly used method for measuring immune cell‑mediated killing is the release assay, where effector cell‑mediated disruption of the target cell membrane results in leakage of its cytoplasmic contents into the culture medium. (technologynetworks.com)