ChimericReceptorsCD28CD134CD27Hepatitis B surface antigenAPCsAntibodiesMicroenvironmentAgonistImmunityIntracellularCellsCytokinesCostimulationTarget antigenLigandAntitumorActivation-inducedTumorsSuperfamilyRecognitionCD19SpecificityExtracellularClinicalInteractsLymphocyteResponsesDendritic cellImmunologicalTCRsAntagonistsTRAF2ProteinsVaccineMiceScFvSurfaceLigationMonoclonalImmune checkpointApoptosis
Chimeric15
- 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)
- 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)
- Take action can be performed with unmanipulated cells or designed cells that express chimeric antigen receptors (CAR-T cells). (azd1152.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)
- Modification with chimeric antigen receptors (CARs) endows T cells with tumor specific cytotoxicity and thus induce anti-tumor immunity against malignancies. (ijbs.com)
- Advances in our understanding on the interaction between the immune system and tumor cells have contributed to the rapid development of novel therapeutic strategies based on chimeric antigen receptor (CAR) or T cell receptor (TCR) modified T cells. (ijbs.com)
- Chimeric antigen receptor (CAR) T-cell therapy is a novel therapeutic T-cell engineering option, where T-cells obtained from a patient's blood are engineered ex vivo to express specific tumour antigen receptors. (cambridgemedicine.org)
- This review includes the biological basis of Chimeric Antigen Receptor (CAR) T-cell therapy as a cancer treatment modality, the opportunities and challenges that CAR T-cell therapy offers, and briefly discusses the role of natural killer (NK) cells in cancer management. (cambridgemedicine.org)
- Chimeric Antigen Receptor (CAR) T-cells are T lymphocytes that have been specifically engineered to target malignant cells. (encyclopedia.pub)
- 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)
- 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)
- [ 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)
- 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)
- 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)
- The agreement is based on one of the improvements to ACT discussed in the December 2011 Nature cancer immunotherapy review , in which autologous T cells isolated from patient blood (not from tumors) are engineered with retroviral vectors carrying chimeric antigen receptors (CARs). (biopharmconsortium.com)
Receptors7
- 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)
- 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)
- 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 response, CAR T-cells have been designed with receptors that can proliferate and retain their function following antigen exposure (6). (cambridgemedicine.org)
- CAR T-cells are T-cells that have been engineered to express receptors that specifically target tumour-associated antigens (8). (cambridgemedicine.org)
- 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)
- Adoptive cell therapy using engineered T-cell receptors (TCRs) targeting cancer-testis antigens, such as Melanoma-associated antigen 3 (MAGE-A3), is a potential approach for the treatment of NSCLC. (thno.org)
CD284
- As a T cell co-stimulator, T cell receptor (TCR) and CD28 signaling causes expression of CD137 on T cell membranes. (wikipedia.org)
- These CAR-T cells contain immune activating domains of CD28 and CD137. (azd1152.com)
- The second-generation CAR T-cells consist of one additional co-stimulatory component (mainly CD28, CD137 or CD134) in the intracellular domain, which amplifies anti-tumour responses in vivo (8). (cambridgemedicine.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)
CD1343
- 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)
- 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)
- 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)
CD272
- CD27, a member of the tumor necrosis factor receptor superfamily, activates NF-κB and stress-activated protein kinase/c-Jun N-terminal kinase via TRAF2, TRAF5, and NF-κB-inducing kinase. (bdbiosciences.com)
- 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)
Hepatitis B surface antigen2
- 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)
- Yu MC, Yuan JM, Ross RK, Govindarajan S. Presence of antibodies to the hepatitis B surface antigen is associated with an excess risk for hepatocellular carcinoma among non-Asians in Los Angeles County, California. (medscape.com)
APCs5
- When T cells are activated by Antigen Presenting Cells (APCs), CD137 becomes embedded in CD4+ and CD8+ T cells. (wikipedia.org)
- The CD137 ligand is a type-II transmembrane glycoprotein expressed on APCs. (wikipedia.org)
- The lymphatic vessels and secondary lymphoid organs (SLOs) are arranged in a manner that optimizes interactions among antigens, APCs, and innate and adaptive effector cells. (jci.org)
- Together, these experiments showed that PD-L1 expression on antigen-presenting cells (APCs) played a role in antitumor T cell responses via PD-1 interactions. (acir.org)
- 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)
Antibodies5
- 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)
- 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)
- Agonistic anti-4-1BB antibodies have been reported to induce T cell mediated antitumor immunity. (bioxcell.com)
- All FcgammaRs can crosslink anti-41BB antibodies to strengthen co-stimulation, but activating FcgammaR-induced antibody-dependent cell-mediated cytotoxicity compromises anti-tumor immunity by deleting 4-1BB(+) cells. (bioxcell.com)
- Antibodies of the IgG sub-class are bi-functional molecules, possessing a F(ab) domain, variable in sequence and responsible for the binding of antigen, and an Fc domain, constant in sequence and responsible for mediating a range of antibody effector functions [ 1 ]. (bmj.com)
Microenvironment4
- 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)
- Nevertheless, targeting solid tumors is more challenging than targeting hematological malignancies because of tumor histopathological characteristics, shortage of specific antigens and local strong immunosuppressive microenvironment [ 4 ]. (ijbs.com)
- However, the tumour may evade immune responses through regulatory T-cell-mediated immune suppression in the tumour microenvironment, defective antigen presentation, and production of immunosuppressive cytokines (5). (cambridgemedicine.org)
- CAR T-cells are specifically designed to target an antigen on the surface of cells and they need to be metabolically fit to reach the tumor, survive in an immunosuppressive microenvironment and display their cytolytic function [ 12 ] . (encyclopedia.pub)
Agonist3
- These immunobiological mechanisms are being utilised for cancer immunotherapy with agonist CD137-binding and crosslinking-inducing agents that elicit CD137 intracellular signaling. (lu.se)
- 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)
- The article, titled "Anticancer immunity induced by a synthetic tumor-targeted CD137 agonist" is available online via this link . (svhealthinvestors.com)
Immunity3
- On the basis of recent advances in the understanding of antitumor immunity, we designed a three-step approach to in situ immunization to lymphoma: (i) inducing immunogenic tumor cell death with the chemotherapeutic drug doxorubicin. (aacrjournals.org)
- 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)
- In additional reports, B cells revised expressing the costimulatory substances genetically, and B cells packed with -galactosylceramide possess synergistically amplified T-cell proliferation as effectively as DCs and induced an array of adaptive immunity against tumor cells [11,12]. (biotech2012.org)
Intracellular4
- 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)
- CAR T-cells consist of an antigen-binding extracellular domain derived from a single chain variable segment (ScFv) of an immunoglobulin, a spacer domain, a transmembrane domain and an intracellular domain (8, 9). (cambridgemedicine.org)
- First-generation CAR T-cells consist only of the TCR-derived CD3ζ intracellular signalling domain, which induces T-cell activation as illustrated in Figure 1 (6, 8). (cambridgemedicine.org)
- Common flow cytometry-based methods used for functional assessment of antigen-specific T cells rely on de novo expression of intracellular cytokines or cell surface activation induced markers. (bvsalud.org)
Cells47
- 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)
- 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)
- 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)
- 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)
- 4-1BB ligand, also known as CD137L, is a 97 kD member of the TNF superfamily present on antigen-presenting cells (dendritic cells and macrophages) and activated B and T lymphocytes. (biolegend.com)
- Efficacy was dependent on the number of CD8+ T cells able to recognize tumor antigens that infiltrated the malignant tissue. (unav.edu)
- LECs are presumably the first cells that come into direct contact with peripheral antigens, cytokines, danger signals, and immune cells travelling from peripheral tissues to lymph nodes. (jci.org)
- Immunologists recognized the importance of lymphatic vessels as channels for leukocyte trafficking from peripheral sites to their draining LNs ( 4 - 6 ), and as conduits for soluble antigens that can be taken up directly by LN-resident B cells and immature DCs ( 7 - 10 ), which help regulate the kinetics of antigen presentation. (jci.org)
- CAR-T cells are impartial of MHCs, and due to transporting costimulatory domains, they could induce strong antitumor responses (2). (azd1152.com)
- A second concern is usually cytokine release syndrome due to the CAR-T cells activation following binding to antigens in both tumor cells and normal cells (226). (azd1152.com)
- 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)
- 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)
- 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)
- However, targeting solid tumors is more challenging than targeting B-cell malignancies with CAR-T cells because of the histopathological structure features, specific antigens shortage and strong immunosuppressive environment of solid tumors. (ijbs.com)
- However, the number of antigen-specific CD8(+) but not CD4(+) T cells declined more rapidly and to a greater extent in c-IAP2(H570A) mice than in WT controls. (bioxcell.com)
- In 1959, Lewis Thomas suggested that the human immune system can recognise tumour-specific antigens on the surface of newly developing tumour cells as 'foreign' and eliminate them (3). (cambridgemedicine.org)
- Recognition of antigens by T-cells is mediated by T-cell receptor (TCR), which binds to peptides presented by Major Histocompatibility Complex (MHC) found on the surface of antigen-presenting cells (6). (cambridgemedicine.org)
- Combinatorial gating of cells expressing activated ß2-integrins and CD137 or CD154 reduced background in unstimulated samples, increasing the signal-to-noise ratio and allowing improved assessment of low-frequency T cell responses. (bvsalud.org)
- CARs are synthetic molecules designed to activate T cells in response to a specific antigen, mimicking T cell activation through the T cell receptor (TCR) and associated costimulatory molecules. (encyclopedia.pub)
- 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)
- 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)
- Compact disc70-T pulsed with multi-antigenic peptide produced multiple antigen-specific polyvalent Compact disc8 T cells which were with the capacity of inhibiting tumor development effectively. (biotech2012.org)
- Our outcomes showed that suffered manifestation of costimulatory substances can boost APC function, as well as the outcomes from mouse tumor versions demonstrate the bigger efficiency of Compact disc8 T cells endowed with costimulatory Compact disc70 in inducing effective antigen-specific Compact disc8 T-cell reactions. (biotech2012.org)
- The aim of the study is to assess whether alterations in the phenotype and function of NK cells induced by the presence of prostate cancer can be detected in the periphery and be used as parameters for aiding diagnosis and assessing disease progression. (ntu.ac.uk)
- The underlying hypothesis of this study was that the presence of prostate cancer would induce detectable changes in the phenotype and function of NK cells in the periphery and that the detection of these would improve the diagnosis and prognosis of prostate cancer. (ntu.ac.uk)
- Priming of NK cells from patients induced a lower induction of CD137 and CRTAM expression, and a greater down-regulation of NKp46 and CD96 expression compared to that which was observed following the priming of NK cells from healthy volunteers. (ntu.ac.uk)
- In this study, we comprehensively screened HLA-A2 restricted MAGE-A3 tumor epitopes and characterized the corresponding TCRs using in vitro artificial antigen presentation cells (APC) system, single-cell transcriptome and TCR V(D)J sequencing, and machine-learning. (thno.org)
- We identified the HLA-A2 restricted T cell epitopes from MAGE-A3 that could effectively induce the activation and cytotoxicity of CD8+ T cells using artificial APC in vitro . (thno.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)
- 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)
- 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)
- Reprogramming is a promising treatment, which redifferentiates T-induced pluripotent stem cells (T-IPSCs) into naïve and cytotoxic T cells or dedifferentiates within their own lineage [ 13 ]. (hindawi.com)
- One is the ability to administer large numbers of highly selected cells with high avidity for tumor antigens that can recognize shared and patient-specific mutated (neo) antigens. (biomedcentral.com)
- In ACT, a physician/researcher extracts a patient's antigen-specific immune cells, which are usually found in tumor tissue. (biopharmconsortium.com)
- This combination regimen also increased the infiltration of CD8+ T-cells that expressed both PD1 and CD137, and these T-cells were shown to express high levels of interferon-gamma, a marker of cytotoxic effector CD8+ T-cells. (amegroups.org)
- The chemo-immunotherapy regimens also increased the number of tumor-infiltrating PD1+CD137+CD8+ T-cells and interferon-gamma-expressing PD1+CD137+CD8+ T-cells, but these increases were not statistically significant. (amegroups.org)
- 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)
- RT-induced damage to cancer cells leads to different outcomes, such as survival, senescence, or death. (nature.com)
Cytokines1
- Site-specific antibody-mediated activation of proapoptotic cytokines: amaize (antibody-mediated apoptosis inducing cytokines) Apr. (quiverquant.com)
Costimulation4
- 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)
- 4-1BBL interacts with 4-1BB (CD137) to induce T and B cell costimulation. (biolegend.com)
- 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)
- CD137 (4-1BB) costimulation maximized clonal expansion and IL-2 was necessary for cytotoxic Th1 differentiation. (uconn.edu)
Target antigen1
- Disease relapse following CAR T cell therapy can be categorized into two major patterns: target antigen loss relapse or antigen-positive relapse. (biomedcentral.com)
Ligand6
- 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 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)
Antitumor1
- CD137 agonists attain immunotherapeutic antitumor effects in cancer mouse models, and multiple agents of this kind are undergoing clinical trials. (unav.edu)
Activation-induced1
- Here, we present a simple method for detection of activated ß2-integrins in combination with established cell surface activation induced markers. (bvsalud.org)
Tumors4
- In mice, this three-step therapy induced CD4- and CD8-dependent systemic immune responses that enhanced T-cell infiltration into distant tumors, leading to their eradication and significantly improving survival. (aacrjournals.org)
- 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)
Superfamily3
- Its alternative names are tumor necrosis factor receptor superfamily member 9 (TNFRSF9), 4-1BB, and induced by lymphocyte activation (ILA). (wikipedia.org)
- The 3H3 monoclonal antibody reacts with mouse 4-1BB, a TNF receptor superfamily member also known as CD137. (bioxcell.com)
- GITR (glucocorticoid-induced TNF receptor family-regulated gene) is a 25 kD TNF receptor superfamily member (also known as AITR and TNFRSF18). (biolegend.com)
Recognition1
- Alloantibody recognition of donor human leukocyte antigen (HLA) is associated with poor clinical transplantation outcomes. (bvsalud.org)
CD191
- In five patients with severe systemic lupus erythematosus (SLE), one-time treatment with a 4-1BB-containing CD19-CAR T cell therapy induced clinical remission of all five patients within three months after treatment, with mild CRS in 3/5 patients and no neurotoxicity observed. (cabalettabio.com)
Specificity2
- However, the high levels of self-antigens present in tumor LHR2A antibody lysates cause the lack of specificity of immune responses and increase the possibility of promoting autoimmune responses, limiting the use of this method in susceptible individuals (220, 221). (azd1152.com)
- However, difficulties such as on-target/off-tumor toxicity and damage to other organs due to the lack of specificity of target antigens are seen. (azd1152.com)
Extracellular1
- Extracellular vesicles (EVs) enable cell-to-cell communication and, by delivering antigens, can stimulate the immune response strongly. (bvsalud.org)
Clinical4
- Several neutralizing TGF- b agents and CD137 agonists are also undergoing early-phase clinical trials. (unav.edu)
- CAR-T therapy can induce rapid and durable clinical responses but is associated with unique acute toxicities. (nature.com)
- The intensity of T-cell response induced by the vaccine was correlated with clinical response. (aacrjournals.org)
- Immunotherapy-based approaches are now inducing long-lasting clinical responses across multiple histological types of neoplasia, in previously difficult-to-treat metastatic cancers. (booksmedicos.org)
Interacts1
- After the binding of the MHC/peptide complex to the TCR, the TCR heterodimer interacts with the antigen and facilitates clustering of the CD3 complex, which mediates further signalling that initiates T-cell activation (6). (cambridgemedicine.org)
Lymphocyte2
- Murine MC are divided into three subsets based on surface expression of lymphocyte antigen 6 complex, locus C (Ly6C) ( 3 , 4 ). (frontiersin.org)
- There is also a need for rational combinations beyond interleukin (IL)-2 and programmed death (PD)-1/ cytotoxic T-lymphocyte-associated antigen (CTLA)-4 immune checkpoint blockade and to combat exhaustion and restore costimulatory functions, e.g., with gene-engineered or pharmacologic agent-treated TILs. (biomedcentral.com)
Responses5
- The objectives of this study were to assess the expression of CXorf61 in TNBCs and healthy tissues and to evaluate its capability to induce T cell responses. (oncotarget.com)
- However, there are notable challenges with CAR T-cell therapy, including non-sustained responses, antigen escape, and life-threatening adverse effects. (cambridgemedicine.org)
- This method should be useful for epitope discovery projects and for the simultaneous monitoring of low-frequency antigen-specific CD4+ and CD8+ T cell responses in various physiological situations. (bvsalud.org)
- To assess the presence of antigen-specific immune responses to a broad panel of candidate tumor antigens. (bcan.org)
- However, systematic analysis of T cell immune responses to MAGE-A3 antigen and corresponding antigen-specific TCR is still lacking. (thno.org)
Dendritic cell2
- CD137 is a costimulatory molecule functioning to stimulate T cell proliferation, dendritic cell maturation, and promotion of B cell antibody secretion. (wikipedia.org)
- Epicutaneous allergen immunotherapy induces a profound and selective modulation in skin dendritic-cell subsets. (ens-lyon.fr)
Immunological2
- Additionally, induced co -expression of luciferase, EGFP, and the melanosomal antigen gp100 facilitates studies on the underlying immunological mechanisms. (unav.edu)
- Following this, in 1971, Sir Frank Mac Farlane Burnet hypothesised that tumour cell antigens induced immunological reaction against cancer and postulated the "immune surveillance theory" (4). (cambridgemedicine.org)
TCRs2
- 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)
- This work identified candidate TCRs potentially suitable for TCR-T design targeting HLA-A2 restricted MAGE-A3 tumor antigen. (thno.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)
TRAF21
- CD137 has been shown to interact with TRAF2. (wikipedia.org)
Proteins2
- Here, we outline a novel methodological approach for generating SARS-CoV-2 vaccine using exosome that delivers antigens from the SARS-CoV-2 structural proteins. (bvsalud.org)
- A pool of long synthetic peptides derived from HPV16 proteins induce objective partial or complete histologic regression of lesions in more than 50% of patients with high-grade vulvar (VuVIN3) and vaginal intraepithelial neoplasia (VaIN3). (aacrjournals.org)
Vaccine3
- Background The pancreatic cancer vaccine, GVAX, induces novel lymphoid aggregates in the otherwise immune quiescent pancreatic ductal adenocarcinoma (PDAC). (bmj.com)
- Engineered EVs can be loaded with viral antigens, thus acting as antigens presenting EVs, eliciting strong and targeted CD8(+) T cell and B cell, offering a unique approach to vaccine development. (bvsalud.org)
- van Poelgeest and colleagues report the ability of ISA 101 vaccine [13 HPV16 E6 and E7 synthetic long peptides mixed with the Montanide adjuvant] without additional treatment to induce objective partial or complete histologic regression of the lesions in more than 50% of patients with high-grade vulvar (VuVIN3) and vaginal intraepithelial neoplasia (VaIN3) with a follow-up of 12 months ( 1 ). (aacrjournals.org)
Mice1
- However, the addi-tion of either recombinant IL-2 or an anti-CD137 mAb markedly improves both outcomes in these mice. (unav.edu)
ScFv1
- 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)
Surface2
- CD137 is only expressed on the cell surface after T cell activation. (wikipedia.org)
- Identification of surface-associated antigens for tumor diagnosis and therapy May. (quiverquant.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)
Monoclonal1
- Monoclonal anti-mouse Compact disc40 (FGK45.5) and anti-4.1BB/CD137 (2A) were prepared from hybridoma tradition supernatants. (biotech2012.org)
Immune checkpoint1
- In this way, CD137 is often referred to as an immune checkpoint. (wikipedia.org)
Apoptosis1
- RT can directly induce cancer cell death through various mechanisms, such as apoptosis, necrosis, and autophagy. (nature.com)