ReceptorsExpressing a chimeric antigen receptorAntibodyChimeric antigen receptor-modifiedReceptor T CellsAgonistTNFRSF9SpecificityCD28CD19Specific tumor antigensCD47Dendritic cellsMembrane proteinAutologousHuman CD137Target antigenCellsAPCsSignal transductionTumorsCD134DifferentiationCD27LymphocytesNormal and malignantTICAStimulationScFvGlycoproteinCostimulationTherapiesSurfaceAntagonistsCancerBindsTransmembraneLigationSecretionCell
Receptors8
- 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)
- Here we demonstrate the discovery of small, chemically synthetic Bicycles that bind to key co-stimulatory receptors and that can be coupled in a modular manner to tumor antigen binding Bicycles to produce tumor localized receptor agonism. (svhealthinvestors.com)
- NK cells contribute to cancer immune surveillance not only by their direct natural cytotoxicity which is triggered rapidly upon stimulation through germline-encoded cell surface receptors, but also by modulating T-cell mediated antitumor immune responses through maintaining the quality of dendritic cells and enhancing the presentation of tumor antigens. (frontiersin.org)
- Furthermore, similar to T cells, specific recognition and elimination of cancer cells by NK cells can be markedly enhanced through expression of chimeric antigen receptors (CARs), which provides an opportunity to generate NK-cell therapeutics of defined specificity for cancer immunotherapy. (frontiersin.org)
- Adoptive T-cell therapy with T cells expressing chimeric antigen receptors (CARs) is an active area of cancer research. (ashpublications.org)
- Human derived T lymphocytes engineered to express chimeric antigen receptors, which are expanded in vitro culture and then infused into patients exerting robust cytotoxicity after tumor antigen recognition and subsequent activation. (biomedcentral.com)
- CAR (Chimeric Antigen Receptor) T cells are T cells that have been engineered with additional receptors to identify specific proteins, called antigens, present on the surface of other cells. (cabalettabio.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)
Expressing a chimeric antigen receptor2
- 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)
- 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)
Antibody5
- CD137 is a costimulatory molecule functioning to stimulate T cell proliferation, dendritic cell maturation, and promotion of B cell antibody secretion. (wikipedia.org)
- ScFv is the antigen-binding domain of CAR structure, which is composed of a single heavy and light chain of monoclonal antibody connected by a linker. (biomedcentral.com)
- Description: ORAI3 Monoclonal Antibody: Antigen stimulation of immune cells triggers Ca++ entry t hrough Ca++ release-activated Ca++ (CRAC) channels. (amjournals.org)
- 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)
- NSCLC known to have a known or likely oncogenic-driver mutation in the EGFR gene, as identified by site local testing or Sponsor central testing Liver disease Positive hepatitis B surface antigen test at screening Patients known to be positive for hepatitis C virus antibody HIV infection, patients are excluded if HIV is not adequately controlled (specific criteria apply). (who.int)
Chimeric antigen receptor-modified2
- 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)
- Cancer immunotherapy by chimeric antigen receptor-modified T (CAR-T) cells has shown exhilarative clinical efficacy for hematological malignancies. (ijbs.com)
Receptor T Cells2
- 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)
- Our CABA™ platform - encompassing Chimeric Antigen Receptor T cells for Autoimmunity (CARTA) and Cabaletta's proprietary Chimeric AutoAntibody Receptor T (CAART) cells - has potential applicability across dozens of autoimmune diseases, including common and severe indications such as systemic lupus erythematosus (SLE), rheumatoid arthritis, myositis and systemic sclerosis. (cabalettabio.com)
Agonist4
- 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)
- 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)
- 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 article, titled "Anticancer immunity induced by a synthetic tumor-targeted CD137 agonist" is available online via this link . (svhealthinvestors.com)
TNFRSF91
- CusabioProtein Description: Extracellular DomainAlternative Name (s) : CD137;ILA;TNFRSF9;4-1BB ligand receptor;CDw137;T-cell antigen. (joplink.net)
Specificity1
- However, due to intricacies of solid tumors and their locations in the human body, treatment of solid tumors with CAR-T cells is facing multiple obstacles, such as the hostile tumor microenvironment, on-tumor/off-tumor toxicities, and undesired antigen specificity [ 2 ]. (ijbs.com)
CD282
- As a T cell co-stimulator, T cell receptor (TCR) and CD28 signaling causes expression of CD137 on T cell membranes. (wikipedia.org)
- 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)
CD194
- 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)
- We used T cells that were retrovirally transduced with this CAR to treat mice bearing a syngeneic lymphoma that naturally expressed the self-antigen murine CD19. (ashpublications.org)
- 12 , 13 Clinical trials in which patients with advanced B-cell malignancies receive T cells expressing anti-CD19 CARs are in early stages, and it is not known whether adoptive transfer of T cells targeting this self-antigen will be an effective therapy for B-cell malignancies. (ashpublications.org)
- The extracellular domain is typically a single-chain variable fragment (scFv) that binds specifically to a target antigen on cancer cells, such as CD19. (cabalettabio.com)
Specific tumor antigens1
- CD8+ T-cell mediated immune responses are important in protection against various pathogens and specific tumor antigens associated with various cancers. (flowmetric.com)
CD473
- Antigens, CD47" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (rush.edu)
- This graph shows the total number of publications written about "Antigens, CD47" by people in this website by year, and whether "Antigens, CD47" was a major or minor topic of these publications. (rush.edu)
- Below are the most recent publications written about "Antigens, CD47" by people in Profiles. (rush.edu)
Dendritic cells4
- 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)
- In addition, CD137 expression is found on dendritic cells, B cells, follicular dendritic cells, natural killer cells, granulocytes and cells of blood vessel walls at sites of inflammation. (kactusbio.cn)
- He is also Leader of the Dendritic Cells (DC) Antigen Presentation research group. (euroacadti.eu)
- His main scientific contributions in the last 10 years relate to antigen presentation in dendritic cells and immunotherapy. (euroacadti.eu)
Membrane protein2
- CD137 is a type I membrane protein and a member of the tumor necrosis factor receptor superfamily. (biolegend.com)
- CD137 ligand (CD137L) is a type II membrane protein and part of the TNF superfamily. (fishersci.com)
Autologous1
- Expanded T cells are screened in stimulations with pathogen proteins in the presence of autologous PBMC as antigen-presenting cells (APC). (antigendiscovery.com)
Human CD1372
- Human CD137 (4-1BB) is expressed on activated T cells within 24-48 hours of activation. (adipogen.com)
- Treatment of C57/Bl6 mice (transgenic for the human CD137 extracellular domain, huCD137) bearing EphA2-expressing MC38 tumors resulted in increased infiltration of CD8+ T cells, the elimination of tumors, and generation of immunological memory. (svhealthinvestors.com)
Target antigen2
- However, relapse of primary disease remains a major obstacle after CAR T cells therapy, and the majority of relapses present a tumor phenotype with retention of target antigen (antigen-positive relapse), which highly correlate with poor CAR T cells persistence. (biomedcentral.com)
- Disease relapse following CAR T cell therapy can be categorized into two major patterns: target antigen loss relapse or antigen-positive relapse. (biomedcentral.com)
Cells37
- 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)
- When T cells are activated by Antigen Presenting Cells (APCs), CD137 becomes embedded in CD4+ and CD8+ T 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)
- 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)
- Cancer cells upregulate cell surface CD137, however the reason behind this remains unclear. (wikipedia.org)
- 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 enables the affected individual's immune system to actively target and kill cancer cells that express CD137 on their cell surfaces. (wikipedia.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)
- CD137L is a co-stimulatory molecule that is expressed on antigen presenting cells (DCs, monocytes/macrophages, B cells) and is upregulated upon activation. (fishersci.com)
- 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)
- 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)
- Efficacy was dependent on the number of CD8+ T cells able to recognize tumor antigens that infiltrated the malignant tissue. (unav.edu)
- 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)
- 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)
- 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)
- 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)
- EphA2), targeting Bicycle potent agonists were created, which activated the costimulatory receptor selectively in the presence of tumor cells expressing that antigen. (svhealthinvestors.com)
- An EphA2/CD137 TICA efficiently co-stimulated human peripheral blood mononuclear cells in vitro in the presence of EphA2-expressing tumor cell lines, as measured by an increased secretion of interferon γ and interleukin-2. (svhealthinvestors.com)
- Here, we discuss effects of the GB tumor microenvironment on NK-cell functionality, summarize early treatment attempts with ex vivo activated NK cells, and describe relevant CAR target antigens validated with CAR-T cells. (frontiersin.org)
- After antigen stimulation, these cells migrate into tissue areas that are inflamed where they exhibit a strong proliferative response and express and release cytokines that help to eliminate infection. (flowmetric.com)
- These are referred to as CD8+ memory T-cells because they 'remember' this previous encounter with the specific antigen, and they are programmed to elicit a faster and stronger immune response to that same antigen. (flowmetric.com)
- A. The linear model describes the activation of naïve T-cells by the presentation of antigen-peptide on major histocompatibility complex (MHC) molecules by the antigen presenting cells (APCs) during the contraction phase of a T-cell response. (flowmetric.com)
- In addition, tumor-associated antigens (TAAs) produced by irradiated tumor cells can be captured by antigen-presenting cells (APCs) in the TME and presented to T cells. (nature.com)
- Most CARs that are being evaluated in current clinical and preclinical studies recognize self-antigens that are expressed by normal tissues as well as malignant cells. (ashpublications.org)
- 4-1BB, is also known as CD137, is a type 2 transmembrane glycoprotein receptor belonging to the TNF superfamily.CD137 can be expressed by activated T cells, but to a larger extent on CD8 than on CD4 T cells. (kactusbio.cn)
- More recent CARs include additional costimulatory domains, such as 4-1BB (CD137), to increase the engineered cells' cytokine production and self-replication for a more durable and potent clinical result. (cabalettabio.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)
- 0.05), suggesting the selective elimination of DCs cross-presenting tumor-associated antigens by iNKT cells. (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)
- Workflows have been developed for the expansion of pathogen-specific CD4 or CD8 T cells expressing CD137, which can then be used in screens against pathogen protein libraries to identify those that specifically activate T cells (e.g. proliferation or cytokine secretion). (antigendiscovery.com)
- Similarly mice engrafted with a melanoma cell line and treated with the vemurafenib analogue PLX4720 also exhibited increased T cell infiltration in tumors and responsiveness to antigens (18 22 The anti-tumor effects of PLX4720 in this engraftment model was particularly dependent on CD8 T cells and could be enhanced by CD137 agonistic mAb treatment suggesting that BrafV600E inhibitors can sensitize tumors to certain immunotherapies (22). (cancer-pictures.org)
- 53% of TNBC patients express this antigen in at least 30% of their tumor cells. (oncotarget.com)
- Furthermore, by in vitro priming of human CD8+ T cells derived from a healthy donor recognizing CXorf61 66-74 we were able to induce a strong antigen-specific immune response and clone a human TCR recognizing this epitope. (oncotarget.com)
- Importantly, the T-box transcription factor Eomesodermin (Eomes) was critical for inducing the cytotoxic marker granzyme B. CD134 plus CD137 dual costimulation also imprinted a cytotoxic phenotype on bystanding CD4 T cells. (uconn.edu)
- Thus, the present study identifies for the first time a specific costimulatory pathway and an intracellular mechanism relying on Eomes that induces both antigen-specific and bystander cytotoxic CD4 Th1 cells. (uconn.edu)
APCs1
- The CD137 ligand is a type-II transmembrane glycoprotein expressed on APCs. (wikipedia.org)
Signal transduction1
- CD137 and its ligand both induce signaling cascades upon interaction, a phenomenon known as bidirectional signal transduction. (wikipedia.org)
Tumors3
- Neoantigens are tumor-specific antigens, which play a critical role in the growth and maintenance of tumors. (nwahomepage.com)
- Tumor target-dependent CD137 agonism using TICAs afforded elimination of tumors in preclinical models using only intermittent dosing, suggesting the potential for a wide therapeutic index in humans. (svhealthinvestors.com)
- For instance tumors treated with BrafV600E inhibitors displayed increased T lymphocyte infiltration and expression of melanoma antigens MHCI and PDL1 expression (17-21). (cancer-pictures.org)
CD1342
- The CD27 antigen is a lymphocyte-specific member of the tumor necrosis factor receptor (TNFR) super family, which also includes nerve growth factor receptor, CD30, CD40, CD95 (Fas), CD120a, CD120b, CD134 (OX 40), and CD137. (bdbiosciences.com)
- This mechanism might be therapeutically useful since CD134 plus CD137 dual costimulation induced CD4 T cell-dependent tumoricidal function in a mouse melanoma model. (uconn.edu)
Differentiation1
- CD137 (4-1BB) costimulation maximized clonal expansion and IL-2 was necessary for cytotoxic Th1 differentiation. (uconn.edu)
CD271
- Camerini D, Walz G, Loenen WA, Borst J, Seed B. The T cell activation antigen CD27 is a member of the nerve growth factor/tumor necrosis factor receptor gene family. (bdbiosciences.com)
Lymphocytes2
- 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)
- A membrane-bound tumor necrosis family member found primarily on activated T-LYMPHOCYTES that binds specifically to CD30 ANTIGEN. (wakehealth.edu)
Normal and malignant1
- Hammarstrom S. The carcinoembryonic antigen (CEA) family: structures, suggested functions and expression in normal and malignant tissues. (wikidoc.org)
TICA1
- and BT7480, a Bicycle TICA™ targeting Nectin-4 and agonizing CD137, in company-sponsored Phase I/II trials. (onenucleus.com)
Stimulation1
- 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)
ScFv2
- 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)
Glycoprotein1
- Carcinoembryonic antigen (CEA) is a glycoprotein involved in cell adhesion . (wikidoc.org)
Costimulation1
- 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)
Therapies1
- In summary, our data confirms this antigen as promising target for T cell based therapies. (oncotarget.com)
Surface2
- CD137 is only expressed on the cell surface after T cell activation. (wikipedia.org)
- Murine MC are divided into three subsets based on surface expression of lymphocyte antigen 6 complex, locus C (Ly6C) ( 3 , 4 ). (frontiersin.org)
Antagonists1
- Ongoing studies are researching CD137 as a biomarker for atherosclerosis as well as CD137 antagonists as potential therapeutics to reduce the symptoms associated with the condition. (wikipedia.org)
Cancer6
- CD137 is also involved in cancer having been found upregulated in cancerous cell lines. (wikipedia.org)
- Methods: Identification of tumour-associated endothelial markers (TEM) by comparing antigen expression on normal vs t-CEC and assess the presence of t-CEC in peripheral blood of cancer patients by incorporating TEM in our novel flow cytometry-based CEC detection assay. (researchgate.net)
- The selection of this first mKRAS (mutant KRAS) lead TCR further validates our capabilities to generate 3S TCRs across both neoantigens and cancer-testis antigens. (nwahomepage.com)
- CD137 agonists attain immunotherapeutic antitumor effects in cancer mouse models, and multiple agents of this kind are undergoing clinical trials. (unav.edu)
- BT8009 is an investigational Bicycle Toxin Conjugate (BTC™) targeting Nectin-4, a well-validated tumor antigen with elevated levels of expression in multiple tumor types, including bladder (urothelial) cancer. (bicycletherapeutics.com)
- 1)Vinay D S , Kwon B S. 4-1BB (CD137), an inducible costimulatory receptor, as a specific target for cancer therapy[J]. BMB Reports, 2014, 47(3):122-129. (kactusbio.cn)
Binds1
- In these studies, Pb-BCY20603, a prototype BRC™ that binds with high affinity to the tumor antigen MT1-MMP and carries a chelate of lead-212, showed potent anti-tumor activity in rodent tumor xenograft studies and achieved complete tumor regressions after 3 dosing cycles of 10 µCi, given two weeks apart. (biospace.com)
Transmembrane1
- CD137 is a 39 kD transmembrane protein also known as 4-1BB. (biolegend.com)
Ligation2
- 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)
Secretion2
- 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)
- A read-out assay such as 3 H-thymidine incorporation or cytokine secretion is used to identify the targets of antigen-specific responses. (antigendiscovery.com)
Cell7
- CD137 appears to be important for T cell proliferation and survival, and induces monocyte activation through its interaction with 4-1BB ligand. (biolegend.com)
- When CD137 interacts with its ligand, it leads to T cell cytokine production and T cell proliferation, among other signaling pathway responses. (wikipedia.org)
- The mechanism connecting CD137 bidirectional signaling to the promotion of atherosclerosis is related to CD137 mediation of epithelial cell damage. (wikipedia.org)
- He has identified a number of different T-cell antigens including survivin, the Bcl-2 family and RhoC. (euroacadti.eu)
- Antigen Discovery Inc., in collaboration with David Koelle's laboratory Laboratory at the University of Washington in Seattle, has developed a high-throughput screening methodology for identification of antigen-specific CD4 and CD8 T cell specificities in cellular samples. (antigendiscovery.com)
- The antigens discovered can be used in downstream applications such as single-cell phenotyping with multiparameter flow cytometry and epitope mapping. (antigendiscovery.com)
- [ 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)