• When CD137 then reacts with the CD137 ligand, it leads to CD137 upregulation. (wikipedia.org)
  • When CD137 interacts with its ligand, it leads to T cell cytokine production and T cell proliferation, among other signaling pathway responses. (wikipedia.org)
  • CD137 and its ligand both induce signaling cascades upon interaction, a phenomenon known as bidirectional signal transduction. (wikipedia.org)
  • The CD137/ligand complex is also involved in regulation of the immune system. (wikipedia.org)
  • The CD137 ligand is a type-II transmembrane glycoprotein expressed on APCs. (wikipedia.org)
  • The CD137 ligand is normally expressed at low levels, but can have increased expression in presence of pathogen associated molecular patterns (PAMPs) or proinflammatory immune responses like IL-1 secretion. (wikipedia.org)
  • CD137/ligand stimulation has been found to lead to stronger anti-tumor responses due to cytotoxic T cell activation and is being examined as a possible anticancer therapy. (wikipedia.org)
  • CD137 appears to be important for T cell proliferation and survival, and induces monocyte activation through its interaction with 4-1BB ligand. (biolegend.com)
  • CD137 ligand (CD137L) is a type II membrane protein and part of the TNF superfamily. (fishersci.com)
  • Type I IFN receptor forms a ternary complex, composed of its two subunits IFNAR1 and IFNAR2, and a type I IFN ligand. (wikidoc.org)
  • Ligand binding to either subunit is required for and precedes dimerization and activation of the receptor. (wikidoc.org)
  • [7] Each type I IFN ligand contains a "hotspot", or a sequence of conserved amino acids that are involved in binding to the receptor, specifically the high affinity receptor IFNAR2, which determines the affinity of each ligand for the receptor. (wikidoc.org)
  • Structural analysis of type I IFN receptor with different type I IFN ligand subtypes revealed a similar binding site for the different agonists. (wikidoc.org)
  • The gene IFNGR1 encodes IFN-γR1, which is the ligand-binding chain (alpha) of the heterodimeric gamma interferon receptor, which is found on macrophages . (wikidoc.org)
  • IFNGR2 , encodes IFN-γR2, the non-ligand-binding partner of the heterodimeric receptor. (wikidoc.org)
  • CusabioProtein Description: Extracellular DomainAlternative Name (s) : CD137;ILA;TNFRSF9;4-1BB ligand receptor;CDw137;T-cell antigen. (joplink.net)
  • The most active T cell endogenous inhibitory pathway is the immunoglobulin superfamily such as CD28/cytotoxic T lymphocyte antigen-4 (CTLA-4): B7-1/B7-2 receptor/ligand grouping, which plays a central role in coordinating immune responses [ 7 , 8 ]. (hindawi.com)
  • The extracellular domain of CD137, comprised of four cysteine-rich domains (CRD-I, CRD-II, CRD-III, CRD-IV), trimerizes upon binding to CD137 ligand (CD137L) to induce cell stimulatory transcriptional and epigenetic changes. (bmj.com)
  • Methods We investigated the molecular and cellular effects of AGEN2373 (CRD-IV-binding, IgG1), a conditionally active CD137-targeting agonist antibody designed to bind and induce CD137 signaling upon FcγR cross-linking while permitting ligand binding to CD137. (bmj.com)
  • Crystal structures of the human 4-1BB receptor bound to its ligand 4-1BBL reveal covalent receptor dimerization as a potential signaling amplifier. (bmj.com)
  • Has received prior therapy with an anti-programmed cell-death 1 (PD-1), anti-programmed cell-death ligand 1 (PD-L1), or anti-programmed cell-death ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. (survivornet.com)
  • Anti-CD137 or anti-CD137L (the ligand of CD137) targeted immunotherapy has been extensively studied, seeking to enhance anticancer immune responses (2). (biocare.net)
  • When T cells are activated by Antigen Presenting Cells (APCs), CD137 becomes embedded in CD4+ and CD8+ T cells. (wikipedia.org)
  • [ 2 ] CRS has become more formally associated with T-cell-engaging immunotherapies, such as blinatumomab and chimeric antigen receptor T-cell (CAR-T) therapy . (medscape.com)
  • TNFSR9) is an activation-induced surface receptor that through costimulation effects provide antigen-primed T cells with augmented survival, proliferation and effector functions as well as metabolic advantages. (lu.se)
  • 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)
  • Ly6C high MC presented downregulated co-stimulatory receptors (CD2, GITR, and TIM1) which direct immune cell proliferation, and upregulated co-stimulatory ligands (LIGHT and SEMA4A) which trigger antigen priming and differentiation. (frontiersin.org)
  • Results: No difference in antigen expression between normal and malignant endothelial cells (ECs) was found for CD54, CD109, CD137, CD141, CD144 and CXCR7. (researchgate.net)
  • Adoptive cell therapy (ACT) with chimeric antigen receptor T (CAR-T) cells can restore the activity of exhausted T cell through reprogramming and is widely used in the treatment of relapsed/refractory (r/r) hematological malignancies. (hindawi.com)
  • We designed a lentiviral vector expressing a chimeric antigen receptor with specificity for the B-cell antigen CD19, coupled with CD137 (a costimulatory receptor in T cells [4-1BB]) and CD3-zeta (a signal-transduction component of the T-cell antigen receptor) signaling domains. (nih.gov)
  • A low dose (approximately 1.5×10(5) cells per kilogram of body weight) of autologous chimeric antigen receptor-modified T cells reinfused into a patient with refractory chronic lymphocytic leukemia (CLL) expanded to a level that was more than 1000 times as high as the initial engraftment level in vivo, with delayed development of the tumor lysis syndrome and with complete remission. (nih.gov)
  • Apart from the tumor lysis syndrome, the only other grade 3/4 toxic effect related to chimeric antigen receptor T cells was lymphopenia. (nih.gov)
  • Engineered cells persisted at high levels for 6 months in the blood and bone marrow and continued to express the chimeric antigen receptor. (nih.gov)
  • This serves as a guidepost for rationally designing new combination checkpoint therapies, downstream T cell receptor (TCR) isolation, cancer antigen identification and molecular characterization of naturally occurring tumor-reactive T cells in human cancer. (upenn.edu)
  • Another approach relies upon the use of chimeric antigen receptors (CARs) that directly target cancer cells or immunosuppressive cellular elements in the tumor microenvironment. (upenn.edu)
  • Adoptive T-cell therapy with anti-CD19 chimeric antigen receptor (CAR)-expressing T cells is a new approach for treating advanced B-cell malignancies. (ashpublications.org)
  • Adoptive T-cell therapy with T cells expressing chimeric antigen receptors (CARs) is an active area of cancer research. (ashpublications.org)
  • Cancer immunotherapy by chimeric antigen receptor-modified T (CAR-T) cells has shown exhilarative clinical efficacy for hematological malignancies. (ijbs.com)
  • CD137 is a costimulatory molecule functioning to stimulate T cell proliferation, dendritic cell maturation, and promotion of B cell antibody secretion. (wikipedia.org)
  • Corticosteroids and anti-cytokine-directed therapy with the anti-IL-6 receptor antibody tocilizumab are effective in mitigating CRS. (medscape.com)
  • The 4B4-1 monoclonal antibody specifically binds to CD137 which is also known as 4-1BB, and ILA (induced by lymphocyte activation). (bdbiosciences.com)
  • 1 2 The investigation of CD137-targeting agonist antibody, urelumab (CRD-I-binding, IgG4), in human subjects showed immunologic and pharmacodynamic effects, but poor efficacy due to dose-limiting liver toxicity. (bmj.com)
  • 3 Preclinical studies using a murine surrogate antibody, clone 3H3 (CRD-I-binding, rIgG2a), also demonstrated hepatotoxicity that correlated with activation of CD137-expressing myeloid cells and memory CD8+ T cells. (bmj.com)
  • 6 7 These and more recent findings implicate epitope and Fc gamma receptor (FcγR)-dependent antibody cross-linking as critical factors for CD137 therapeutic antibody design. (bmj.com)
  • The role of epitope and FcγR binding as critical factors for anti-CD137 therapeutic activity were elucidated in primary cell-based assays and syngeneic tumor-bearing mouse models using anti-mouse antibody clones S3B1 (CRD-IV-binding) and 3H3, surrogates of AGEN2373 and urelumab, respectively. (bmj.com)
  • Results AGEN2373 bound with high-affinity to CD137 CRD-IV and promoted potent agonist activity of CD137 that was conditionally dependent on Fc-dependent antibody cross-linking. (bmj.com)
  • Want to Learn More About CD137 Antibody? (biocare.net)
  • Boosting cancer immunotherapy with anti-CD137 antibody therapy. (biocare.net)
  • Most of these immunomodulatory antibodies are of IgG isotypes that have low, or no, binding to the Fc gamma receptors (FcγRs) that trigger cell-mediated cytotoxic effector functions such as antibody dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP). (bmj.com)
  • The 3H3 monoclonal antibody reacts with mouse 4-1BB, a TNF receptor superfamily member also known as CD137. (bioxcell.com)
  • Its alternative names are tumor necrosis factor receptor superfamily member 9 (TNFRSF9), 4-1BB, and induced by lymphocyte activation (ILA). (wikipedia.org)
  • It is encoded by TNFRSF9 (tumor necrosis factor receptor superfamily, member 9). (bdbiosciences.com)
  • CD137 (4-1BB), or tumor necrosis factor receptor superfamily member 9 (TNFRSF9), is a promising target for enhancing antitumor immune responses without the autoimmune side effects associated with immunotherapy approaches (1). (biocare.net)
  • CD137 is a type I membrane protein and a member of the tumor necrosis factor receptor superfamily. (biolegend.com)
  • Death receptor 6 ( DR6 ), also known as tumor necrosis factor receptor superfamily member 21 ( TNFRSF21 ), is a cell surface receptor of the tumor necrosis factor receptor superfamily which activates the JNK and NF-κB pathways. (wikidoc.org)
  • The protein encoded by this gene is a member of the TNF-receptor superfamily. (wikidoc.org)
  • NK cell activation and the triggering of effector functions is governed by a complex set of activating and inhibitory receptors. (frontiersin.org)
  • Through its death domain , this receptor interacts with TRADD protein, which is known to serve as an adaptor that mediates signal transduction of TNF-receptors. (wikidoc.org)
  • When the CD137/CD137L complex interacts with endothelial cells, including those lining vascular structures, it induces the upregulation of molecules that promote inflammation and damage. (wikipedia.org)
  • Its receptor, CD137/4-1BB, is found on a variety of cells, including inflamed endothelial cells, where its expression enhances extravasation of CD137L expressing monocytes. (fishersci.com)
  • Activated T cells also express CD137, and engagement with CD137L enhances T cell proliferation, IL-2 secretion, survival, and cytotoxic activity. (fishersci.com)
  • CD137 (4-1BB) is a member of the TNFR family that mediates potent T cell costimulatory signals upon ligation by CD137L or agonist monoclonal antibodies (mAbs). (unav.edu)
  • 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)
  • CD137, a member of the tumor necrosis factor (TNF) receptor family, is a type 1 transmembrane protein, expressed on surfaces of leukocytes and non-immune cells. (wikipedia.org)
  • Tumor necrosis factor (TNF) receptor shedding controls thresholds of innate immune activation that balance opposing TNF functions in infectious and inflammatory diseases. (southernbiotech.com)
  • CD137 is a type I transmembrane glycoprotein that belongs to the TNF/NGF receptor family. (bdbiosciences.com)
  • CD137 plays roles in the costimulation, differentiation and survival of T cells and B cells. (bdbiosciences.com)
  • In this study, side-by-side comparisons show that provision of CD137 costimulation in-cis with regard to the TCR-CD3-ligating cell is superior to that provided in-trans in terms of T cell activation, proliferation, survival, cytokine secretion and mitochondrial fitness in mouse and human. (lu.se)
  • Here we report that the superiority of cis versus trans CD137-costimulation is readily observed in vivo and is relevant for understanding the immunotherapeutic effects of CAR T cells and CD137 agonistic therapies currently undergoing clinical trials, which may provide costimulation either in cis or in trans. (lu.se)
  • Moreover, cIAPs are required for CD137 signaling toward the NF-?B and MAPK pathways and for costimulation of human and mouse T lymphocytes. (unav.edu)
  • NMR structure of the interferon-binding ectodomain of the human interferon receptor. (wikidoc.org)
  • Toll-like receptors (TLRs) and receptor for advanced glycation end products (RAGE) and their ligands were all found to play a key role in inflammation. (shengsci.com)
  • About half of the genes and proteins specifically present in preterm birth have the properties of endogenous ligands "alarmin" for receptor activation. (shengsci.com)
  • What is known is the fact that mAbs targeting CD137 are successful in fighting cancer as they can not only mark cancer cells, but they allow for CD8+ T cell activation and increased IFN-gamma secretion as per CD137's function as a costimulatory molecule. (wikipedia.org)
  • This protein pairs with the receptor molecule IL-12Rβ1 ( IL12RB1 ), together forming the IL-23 receptor complex, and both are required for IL-23 signaling. (wikidoc.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)
  • The interferon-α/β receptor (IFNAR) is a virtually ubiquitous membrane receptor which binds endogenous type I interferon (IFN) cytokines. (wikidoc.org)
  • LECs can modulate dendritic cell function, present antigens to T cells on MHC class I and MHC class II molecules, and express immunomodulatory cytokines and receptors, which suggests that their roles in adaptive immunity are far more extensive than previously realized. (jci.org)
  • In this study, a member of the tumour necrosis factor receptor (TNFR)-family, CD137 (4-1BB) was investigated for its potential to identify the total pool of circulating alloreactive T cells. (eur.nl)
  • CD137 is a 39 kD transmembrane protein also known as 4-1BB. (biolegend.com)
  • In conclusion, activation-induced CD137 expression is a fast assay allowing for detection and functional analysis of the total alloreactive T cell compartment at the single-cell level by multi-parameter flow cytometry. (eur.nl)
  • CD137 agonists attain immunotherapeutic antitumor effects in cancer mouse models, and multiple agents of this kind are undergoing clinical trials. (unav.edu)
  • Several neutralizing TGF- b agents and CD137 agonists are also undergoing early-phase clinical trials. (unav.edu)
  • IFNAR is a heteromeric cell surface receptor composed of two subunits, referred to as the low affinity subunit, IFNAR1 , and the high affinity subunit, IFNAR2 . (wikidoc.org)
  • The protein encoded by this gene is a subunit of the receptor for IL-23 . (wikidoc.org)
  • RESULTS: We identified GluN2C as the most abundant subunit of the NMDA receptor expressed in the VTA. (bvsalud.org)
  • LIGHT binds to two different receptors, Herpes Virus Entry Mediator (HVEM) and Lymphotoxin beta Receptor (LTβR). (amjournals.org)
  • As a T cell co-stimulator, T cell receptor (TCR) and CD28 signaling causes expression of CD137 on T cell membranes. (wikipedia.org)
  • Transferred T cells that persist in the blood and form memory have a phenotype consistent with a less differentiated state (CD27/CD28/IL-7 receptor-α) [ 3 ]. (biomedcentral.com)
  • To make the most of these approaches, we have constructed chimeric mRNAs encoding single-chain IL-12 fused to single-chain fragment variable (scFv) antibodies that bind to transforming growth factor b (TGF-b) and CD137 (4-1BB). (unav.edu)
  • To attain TGF-beta and CD137 binding by the constructions, we used bispecific tandem scFv antibodies (taFvs) derived from the specific 1D11 and 1D8 monoclonal antibodies (mAbs), respectively. (unav.edu)
  • Specific antibodies against CD137 are currently in clinical trials aiming to activate and enhance anti-cancer immune responses as well as suppress oncogenic cells (3). (biocare.net)
  • Ly6C high MC exhibited activated neutrophil degranulation, lysosome, cytokine production/receptor interaction and myeloid cell activation pathways, and Ly6C low MC presented features of lymphocyte immunity pathways in both mice. (frontiersin.org)
  • Antitumor effects of agonist anti-CD137 mAbs are critically dependent on the integrity of cIAPs in cancer mouse models, and cIAPs are also required for signaling from CARs encompassing CD137's cytoplasmic tail. (unav.edu)
  • [2] The DR6 is an alpha-helical integral membrane receptor protein that shows evidence that it has something to do with the inhibition of blood vessels forming on tumors which would allow them to grow larger. (wikidoc.org)
  • Interferon gamma receptor 1 ( IFNGR1 ) also known as CD119 ( C luster of D ifferentiation 119 ), is a protein that in humans is encoded by the IFNGR1 gene . (wikidoc.org)
  • One approach relies on the isolation and cloning of T cell receptors (TCRs) that confer non-reactive T cells with specific and potent immune function following gene transfer. (upenn.edu)
  • Death receptor 6 gets a chemical message and starts a signaling pathway that causes apoptosis, also known as cell death, to occur. (wikidoc.org)
  • CD137 is also involved in cancer having been found upregulated in cancerous cell lines. (wikipedia.org)
  • Cancer cells upregulate cell surface CD137, however the reason behind this remains unclear. (wikipedia.org)
  • This enables the affected individual's immune system to actively target and kill cancer cells that express CD137 on their cell surfaces. (wikipedia.org)
  • These immunobiological mechanisms are being utilised for cancer immunotherapy with agonist CD137-binding and crosslinking-inducing agents that elicit CD137 intracellular signaling. (lu.se)
  • The selective expression of CD137 on cells of the immune system and oncogenic cells in several types of cancers including breast, melanoma and lymphoma leads CD137 to be an attractive target for cancer immunotherapy. (biocare.net)
  • CD137, an attractive candidate for the immunotherapy of lung cancer. (biocare.net)
  • Other cells that express CD137 include both immune cells (i.e. monocytes, natural killer cells, dendritic cells, follicular dendritic cells (FDCs), and regulatory T cells) and non-immune cells (i.e. chondrocytes, neurons, astrocytes, microglia and endothelial cells). (wikipedia.org)
  • Cross-linking CD137 and active T cells can not only result in T cell proliferation via increased IL-2 secretion, but surviving cells also contribute to expanding immune system memory and augmenting T cell cytolytic activity. (wikipedia.org)
  • Treatments designed to target the CD137 molecules expressed on immune cell surfaces often lead to T cell proliferation as CD137 stimulation allows for the T cells to continue through the cell cycle. (wikipedia.org)
  • Summary: Detection and isolation of viable alloreactive T cells at the single-cell level requires a cell surface marker induced specifically upon T cell receptor activation. (eur.nl)
  • Optimal conditions for sensitive and specific detection of allogeneic-induced CD137 expression on circulating T cells were established. (eur.nl)
  • Upon allogeneic (re-)stimulation, the cytokine-producing as well as proliferative capacity of T cells resided mainly within the CD137-expressing fraction. (eur.nl)
  • CD137 signaling plays a significant role in multiple cells and regulates the activity of many immune cells. (biocare.net)
  • In this way, CD137 is often referred to as an immune checkpoint. (wikipedia.org)
  • Utomilumab (PF-05082566) targets this receptor to stimulate a more intense immune system attack on cancers. (wikipedia.org)
  • Cis ligation of CD137 relative to the TCR-CD3. (lu.se)
  • Cis ligation of CD137 relative to the TCR-CD3 complex results in more intense canonical and non-canonical NF-κB signaling and provides a more robust induction of cell cycle and DNA damage repair gene expression programs. (lu.se)
  • This receptor has been shown to activate NF-κB and MAPK8 / JNK , and induce cell apoptosis . (wikidoc.org)
  • CD137 is only expressed on the cell surface after T cell activation. (wikipedia.org)
  • The mechanism connecting CD137 bidirectional signaling to the promotion of atherosclerosis is related to CD137 mediation of epithelial cell damage. (wikipedia.org)
  • Background CD137 (4-1BB) represents a costimulatory pathway that promotes T, NK, and dendritic cell effector functions favorable for antitumor immunity. (bmj.com)
  • 4-1BB is a TNF receptor family member that signals via a complex that includes TRAF family members and the c-IAPs to upregulate NF-kappaB and ERK, and has been implicated in memory T-cell survival. (bioxcell.com)
  • Interferon gamma receptor 1 has been shown to interact with Interferon-gamma . (wikidoc.org)
  • The human interferon-gamma receptor. (wikidoc.org)