• A2AR & A2BR: The Adenosine A2A receptor is regarded as an important checkpoint in cancer therapy because adenosine in the immune microenvironment, leading to the activation of the A2a receptor, is negative immune feedback loop and the tumor microenvironment has relatively high concentrations of adenosine. (wikipedia.org)
  • These TCRs will be combined with the PD1-41BB and/or the CD40L-CD28 costimulatory switch proteins to enhance penetration, proliferation, persistence and enhanced cytotoxic function of Medigene's TCR-T cells while mitigating the immunosuppressive effects of the tumor microenvironment. (nwahomepage.com)
  • While GB tumors are frequently infiltrated by natural killer (NK) cells, these are actively suppressed by the GB cells and the GB tumor microenvironment. (frontiersin.org)
  • 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, the composition of the immunologic tumor microenvironment undergoes changes upon radiotherapy, chemotherapy, or even after anti-angiogenic therapy ( 6 ). (frontiersin.org)
  • Although RT is an important modality for cancer treatment, the consequential changes caused by RT in the tumor microenvironment (TME) have not yet been fully elucidated. (nature.com)
  • Furthermore, inflammatory mediators released by irradiated dying cells can attract and regulate immune cells in the tumor microenvironment (TME), further killing cancer cells. (nature.com)
  • While inflammatory injury drives both fibrogenesis and carcinogenesis, the tolerogenic microenvironment of the liver conveys immunosuppressive effects that encourage tumor growth. (mdpi.com)
  • While LIGHT binding to HVEM delivers a co-stimulatory signal to T cells (1), LIGHT binding to LTβR is critical for the formation of lymphoid structures which can stimulate T cell infiltration and activation of a tumor microenvironment, leading to rapid T cell-mediated tissue destruction (2). (amjournals.org)
  • 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)
  • In this landscape, most studies have primarily focused on improving CAR-T cells and overcoming the unfavorable effects of tumor microenvironment on solid tumors. (ijbs.com)
  • 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)
  • The BrafV600E mutation has a direct role in driving cellular transformation but multiple studies suggest that it also indirectly modulates the tumor microenvironment. (cancer-pictures.org)
  • Thus more investigation is needed to better characterize the nature of the tumor microenvironment in melanoma and how BrafV600E inhibitors affect the function of infiltrating. (cancer-pictures.org)
  • More abundant CD8 + T lymphocytes were found in B16-OVA tumor-draining lymph nodes and in the tumor microenvironment following intratumoral BO-112 treatment, with enhanced numbers of tumor antigen-specific cytotoxic T lymphocytes. (polyplus-sartorius.com)
  • In situ immunization aims at generating antitumor immune responses through manipulating the tumor microenvironment. (aacrjournals.org)
  • The microenvironment of a developing tumor is composed of proliferating cancer cells, blood vessels, stromal cells, infiltrating inflammatory cells, and a variety of associated tissue cells. (nutriforce.cn)
  • Accumulating data also suggest that hypoxic stress in the tumor microenvironment promotes tumor escape mechanisms through the emergence of immune-resistant tumor variants and immune suppression. (nutriforce.cn)
  • Thus, solid tumors seem to build up a hostile hypoxic microenvironment that hampers cell-mediated immunity and dampen the efficacy of the immune response. (nutriforce.cn)
  • The RAS plays a crucial role in cancer biology and affects tumor growth and dissemination directly and indirectly by remodeling the tumor microenvironment. (nutriforce.cn)
  • 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)
  • MDSCs and M2 macrophages) and increased the population of CD8 + T cells and monocytes within the tumor microenvironment (TME). (acir.org)
  • 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)
  • 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)
  • 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)
  • 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)
  • Take action can be performed with unmanipulated cells or designed cells that express chimeric antigen receptors (CAR-T cells). (azd1152.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)
  • 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)
  • 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)
  • 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)
  • In contrast to other cancers such as adenocarcinomas of the lung or melanoma, primary brain tumors like GB and low grade gliomas (LGG) are known as rather immunologically "cold" tumors, typically with low numbers of tumor-infiltrating lymphocytes (TILs) ( 4 ), and the mere amount of TILs is not associated with patient survival ( 5 ). (frontiersin.org)
  • 4 According to the number of tumor-infiltrating lymphocytes, tumors can be divided into three phenotypes: immune-inflamed, immune-excluded, and immune-desert types. (nature.com)
  • Poly I:C is a powerful immune adjuvant as a result of its agonist activities on TLR-3, MDA5 and RIG-I. BO-112 is a nanoplexed formulation of Poly I:C complexed with polyethylenimine that causes tumor cell apoptosis showing immunogenic cell death features and which upon intratumoral release results in more prominent tumor infiltration by T lymphocytes. (polyplus-sartorius.com)
  • In one study, tumor-infiltrating lymphocytes (TILs) were collected from metastatic lesions of a patient transporting KRAS-G12D mutation. (azd1152.com)
  • Cell-mediated immune responses are initiated by T lymphocytes that are themselves stimulated by cognate peptides bound to MHC molecules on antig en-presenting cells (APC). (thermofisher.com)
  • Tumor infiltrating lymphocytes (TILs) in a colorectal carcinoma. (biopharmconsortium.com)
  • Such cells are known as "tumor infiltrating lymphocytes" (TILs). (biopharmconsortium.com)
  • By combining all our TCRs with our PD1-41BB or CD40L-CD28 costimulatory switch proteins, we remain convinced that our approach will consistently deliver best-in-class TCR-T therapies leading to improved outcomes for patients suffering from difficult-to-treat solid tumors. (nwahomepage.com)
  • Despite the progresses made in treating hematological malignancies, challenges still remain for use of CAR-T cell therapy to treat solid tumors. (ijbs.com)
  • To further understand the current status and trend for developing CAR-T cell based therapies for various solid tumors, this review emphasizes on CAR-T techniques, current obstacles, and strategies for application, as well as necessary companion diagnostics for treatment of solid tumors with CAR-T cells. (ijbs.com)
  • Encouragingly and optimistically, in this landscape, more than forty clinical trials in treatment of solid tumors by CAR-T cells have been registered in China alone (Table 1 ) [ 6 ]. (ijbs.com)
  • Therefore, in this review, we focus on current CAR-T techniques , obstacles, strategies for overcoming these obstacles, as well as necessary companion diagnostics in treatment of solid tumors with CAR-T cells. (ijbs.com)
  • It is widely accepted that hypoxic stresses occur in most solid tumors. (nutriforce.cn)
  • CXCL8) is produced by many solid tumors, where it attracts myeloid cells and potentiates the survival of tumor cells. (acir.org)
  • After deploying Medigene's proprietary algorithms for evaluation of the unique characteristics of each of the 3S TCRs, including peptide specificity, tumor cell recognition and off-target toxicity, the Company has prioritized one of the 3S TCRs as the lead to move forward to the pre-clinical stage for Medigene's MDG2011 program. (nwahomepage.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)
  • 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)
  • The earliest CARs consisted of an extracellular antigen recognition domain (typically a single chain Fv variable fragment from a monoclonal antibody) linked via a transmembrane domain to an intracellular signaling domain (usually the CD3ζ endodomain), resulting in the redirection of T-cell specificity toward target antigen-positive cells. (ashpublications.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)
  • Activated T cells also express CD137, and engagement with CD137L enhances T cell proliferation, IL-2 secretion, survival, and cytotoxic activity. (fishersci.com)
  • The CAR-containing exosomes express a high level of cytotoxic molecules and inhibit tumour growth. (nature.com)
  • In vitro , doxorubicin microparticles were less cytotoxic to DCs than to B lymphoma cells, did not require internalization by tumor cells, and significantly enhanced phagocytosis of tumor cells by DCs as compared with soluble doxorubicin. (aacrjournals.org)
  • Cytotoxic CD4 Th1 cells are emerging as a therapeutically useful T cell lineage that can effectively target tumors, but until now the pathways that govern their differentiation have been poorly understood. (uconn.edu)
  • CD137 (4-1BB) costimulation maximized clonal expansion and IL-2 was necessary for cytotoxic Th1 differentiation. (uconn.edu)
  • 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)
  • Four stimulatory checkpoint molecules are members of the tumor necrosis factor (TNF) receptor superfamily-CD27, CD40, OX40, GITR and CD137. (wikipedia.org)
  • 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)
  • CD137 is a type I membrane protein and a member of the TNF receptor superfamily. (adipogen.com)
  • TNFRSF9, also known as 4-1BB and CD137, is a member of the tumor necrosis factor receptor superfamily (TNFRSF). (biolegend.com)
  • The 3H3 monoclonal antibody reacts with mouse 4-1BB, a TNF receptor superfamily member also known as CD137. (bioxcell.com)
  • 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)
  • In the context of mCRC, CAR-T cells as monotherapy or in combination with cytokines such as IL-12 had encouraging effects such as tumor reduction and long-term disease Vanin-1-IN-1 stability in some Vanin-1-IN-1 patients (222C225). (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)
  • These collaborations enable us to advance a broad pipeline of partnered and wholly owned BRCs that represents the third pillar of our oncology strategy beyond our Bicycle toxin conjugate (BTC™) and Bicycle tumor-targeted immune cell agonist® ( Bicycle TICA™) programs. (biospace.com)
  • commented, "I have been following the Bicycle story since covering them as a research analyst on the sell-side, and have been especially impressed by the recent clinical progress the team has made across their platform, from the Bicycle toxin conjugate (BTC™) and Bicycle tumor-targeted immune cell agonist® (Bicycle TICA™) programs, to the newer addition of Bicycle® radio-conjugates (BRCs). (onenucleus.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)
  • 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)
  • Approaching the response issue from the other direction, Dr. Melero discussed invigorating T cell function using an agonist of the costimulatory receptor CD137, particularly in combination with other immunotherapies, such as ICB or adoptive T cell transfer. (acir.org)
  • 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)
  • It has been shown that targeted delivery of LIGHT to tumors, thereby causing the T cell infiltration of the tumor, can enhance the response of the PD-1/PD-L1 checkpoint blockade anti-cancer therapy (3), suggesting that LIGHT may become a potent tool in anti-cancer treatment. (amjournals.org)
  • 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)
  • 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)
  • In contrast another study concluded that PLX4720 decreased T cell infiltration in the tumors and were unable to enhance anti-tumor responses in conjunction with CTLA4 blockade (23). (cancer-pictures.org)
  • 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)
  • The engineering of CAR-T cells is unique in that T cells are collected from a patient and genetically modified to express a receptor that will bind to a surface antigen expressed on the patient's own tumor cells. (ashpublications.org)
  • 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)
  • [ 5 ] In addition, immunoglobulin and vaccination should be administered to newborns born to women positive for hepatitis B surface antigen (HBsAg). (medscape.com)
  • Flow cytometry analysis of tumor infiltrating T-cells in a murine model of PDAC was performed to investigate the therapeutic effects and mechanism of anti-CSF-1R/anti-PD-1/GVAX combination immunotherapy. (bmj.com)
  • Immune-inflamed tumors are called hot tumors, while the latter two are collectively referred to as cold tumors, and they respond poorly to immunotherapy. (nature.com)
  • Cancer immunotherapy by chimeric antigen receptor-modified T (CAR-T) cells has shown exhilarative clinical efficacy for hematological malignancies. (ijbs.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)
  • The growth of such advanced techniques along with the neoantigen-based immunotherapy could herald a new era in treating heterogeneous tumors such as CRC. (azd1152.com)
  • 4.2 Adoptive T Cell Therapy Take action is a malignancy immunotherapy method in which T cells are collected from your tumor, lymph nodes, or peripheral blood of a patient and returned Vanin-1-IN-1 to the patients body after proliferation and selection of tumor-specific T cells. (azd1152.com)
  • Immunotherapy with monoclonal antibodies may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. (bcan.org)
  • We review clinical data on the benefit of RASi in primary and metastatic tumors and propose that, by activating immunostimulatory pathways, these inhibitors can enhance immunotherapy of cancer. (nutriforce.cn)
  • As a proof of this concept, we have developed LVGN6051, a humanized 4-1BB mAb-AG that shows high anti-tumor efficacy in the absence of liver toxicity in a mouse model of cancer immunotherapy. (bioxcell.com)
  • Combination of Adar1 loss and anti-PD-1 synergized to eliminate tumors and prolong survival in mice, and Adar1 deletion resensitized treatment-resistant tumors to immunotherapy, even in the case when tumor cells could not be recognized by CD8 + T cells due to B2m loss. (acir.org)
  • After treatment, tumor-specific T cells from mice treated with neoadjuvant immunotherapy had an increased expression of granzyme B, TNFα, and IFNγ. (acir.org)
  • On the second day of the conference, Ignacio Melero presented the Keynote Address on the importance of IL-8 and CD137 (4-1BB) in immunotherapy. (acir.org)
  • GVAX also upregulates the PD-1/PD-L1 pathway, and a pre-clinical model demonstrated the anti-tumor effects of combination GVAX and anti-PD-1 antibody therapy (GVAX/αPD-1). (bmj.com)
  • 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)
  • Description: LIGHT Antibody: LIGHT, also known as Tumor Necrosis Factor Superfamily member 14 (TNFSF14), is a co-stimulatory molecule that can regulate T-cell activation (1) and has recently been identified as an immune checkpoint protein. (amjournals.org)
  • 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)
  • Supporting this result agonistic CD40 antibody was sufficient to evoke anti-tumor immunity and suppress tumor growth in tumor-bearing mice. (cancer-pictures.org)
  • In vivo studies with TNFSF9 knockout mice and with the agonistic anti-TNFRSF9 monoclonal antibody showed that TNFRSF9/TNFSF9 interaction keeps optimal CD8 T-cell mediated immune response against viral infections and tumors. (biolegend.com)
  • Costimulation of T cell responses with monoclonal antibody agonists (mAb-AG) targeting 4-1BB showed robust anti-tumor activity in preclinical models, but their clinical development was hampered by low efficacy (Utomilumab) or severe liver toxicity (Urelumab). (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)
  • CD27: This molecule supports antigen-specific expansion of naïve T cells and is vital for the generation of T cell memory. (wikipedia.org)
  • 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)
  • 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)
  • 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)
  • 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 ligand for GITR is mainly expressed on antigen presenting cells. (wikipedia.org)
  • 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)
  • 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)
  • 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)
  • Alloantibody recognition of donor human leukocyte antigen (HLA) is associated with poor clinical transplantation outcomes. (bvsalud.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)
  • 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)
  • Haining concluded that Adar1 is a checkpoint, and its removal could potentially induce sufficient inflammation to restrict tumor growth while bypassing the need for recognition of tumor by CD8 + T cells. (acir.org)
  • These CAR-T cells contain immune activating domains of CD28 and CD137. (azd1152.com)
  • Second generation CAR-T cells, with the addition of costimulatory domains including CD28, 4-1BB, or OX40 to the intracellular portion, are engineered to enhance cytokine secretion and effector cell expansion, and prevent activation-induced apoptosis and immune suppression by tumor-related metabolites. (ashpublications.org)
  • CD40: This molecule, found on a variety of immune system cells including antigen presenting cells has CD40L, otherwise known as CD154 and transiently expressed on the surface of activated CD4+ T cells, as its ligand. (wikipedia.org)
  • CD137-mediated signaling is also known to protect T cells, and in particular, CD8+ T cells from activation-induced cell death. (wikipedia.org)
  • OX40's value as a drug target primarily lies in the fact that, being transiently expressed after T-cell receptor engagement, it is only upregulated on the most recently antigen-activated T cells within inflammatory lesions. (wikipedia.org)
  • PDF) Kraan J, van den Broek P, Verhoef C, Grunhagen DJ, Taal W, Gratama JW, Sleijfer SEndothelial CD276 (B7-H3) expression is increased in human malignancies and distinguishes between normal and tumour-derived circulating endothelial cells. (researchgate.net)
  • 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)
  • Efficacy was dependent on the number of CD8+ T cells able to recognize tumor antigens that infiltrated the malignant tissue. (unav.edu)
  • 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)
  • However, CAR-T cells can also produce some adverse events after treatment of hematological malignancies, such as cytokine release syndrome (CRS), neurotoxicity, and on-target/off-tumor toxicity, which may cause systemic immune stress inflammation, destruction of the blood-brain barrier, and even normal tissue damage. (hindawi.com)
  • Various biological processes including immunoreaction of infection, tumor prevention, and human aging could cause telomere damage, tumor-related stress responses, and T regulatory (Treg) cells activation, which even trigger T cell senescence showing the distinctive phenotypic and functional alternation [ 9 , 10 ]. (hindawi.com)
  • 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)
  • 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)
  • 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)
  • 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)
  • Therefore, study on factors and mechanisms that limit the in vivo persistence of CAR T cells is crucial for developing strategies to reduce the probability of tumor relapse and improve the long-term disease-free survival for patients who are treated with CAR T cells. (biomedcentral.com)
  • One focus of the Powell lab is on the generation/isolation high avidity, tumor-reactive T cells from heterogenous tumor infiltrating lymphocyte populations in traditionally "non-immunogenic" cancers utilizing novel T cell capture techniques, and to deeply examine the characteristics and function of these immune cells. (upenn.edu)
  • 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 field of study is the de novo generation of tumor-reactive T cells through genetic engineering methods. (upenn.edu)
  • Other current efforts include the exploration of immunomodulation to potentiate endogenous antitumor T cell responses, use of bispecific antibodies, pharmacological sensitization of tumor cells to immune attack, tumor vasculature targeting, preclinical validations, clinical translation and trial support. (upenn.edu)
  • Despite these efforts, there are still no CAR-T cells clinically approved for solid tumor treatment so far. (ijbs.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)
  • In addition to blocking anti-tumor immune responses these immunomodulatory cells can also promote tumor growth and metastasis through secretion of angiogenic factors (e.g. (cancer-pictures.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)
  • 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)
  • A, Representative flow plots and MFI of 4-1BB expression on splenic and tumor CD4+ T cells in HuT mice (n = 5) with large 200 mm3 tumors treated with 5 mg/kg of CD3-binding control or PSMAxCD3 48 hours after dose. (lyvgen.cn)
  • E, Total counts of tumor-infiltrating granzyme B+ CD8+ T cells after treatment administration examined by flow cytometry. (lyvgen.cn)
  • H, Individual tumor growth curves from mice reimplanted with TRAMP-C2-hPSMA cells 35 days after initial tumor clearance. (lyvgen.cn)
  • I, Individual tumor growth curves of TRAMP-C2 cells that were implanted 50 days after initial tumor clearance. (lyvgen.cn)
  • Tumor cells (1.5-2 × 105) were seeded on specific 8-well plates to measure electric impedance. (polyplus-sartorius.com)
  • Doxorubicin enhances the expression of "eat-me" signals by dying tumor cells, facilitating their phagocytosis by dendritic cells (DC). (aacrjournals.org)
  • and or tumor cells infected with oncolytic viruses release PAMPs, which increases immune responses (217, 218). (azd1152.com)
  • The results of phase I and II trials showed that the use of Newcastle virus-infected tumor cells reduced recurrence and increased OS in CRC patients (44, 219). (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)
  • The use of tumor-specific unmanipulated cells has also yielded positive results in CRC. (azd1152.com)
  • Evidence reported to date suggests overlapping functions for these ligands and their constitutive expression on some normal tissues and upregulation on activated antigen-presenting cells. (thermofisher.com)
  • In ACT, a physician/researcher extracts a patient's antigen-specific immune cells, which are usually found in tumor tissue. (biopharmconsortium.com)
  • The infused T cells traffic to tumors and can mediate their destruction. (biopharmconsortium.com)
  • Human CD137 (4-1BB) is expressed on activated T cells within 24-48 hours of activation. (adipogen.com)
  • The crosstalk between stromal cells and malignant cells within this environment crucially determines the fate of tumor progression, its hostility, and heterogeneity. (nutriforce.cn)
  • Moreover, cancer cells found within hypoxic regions are presumed to represent the most aggressive and therapy-resistant fractions of the tumor. (nutriforce.cn)
  • In this issue of Blood , Brentjens and colleagues report on the feasibility, tolerability, and persistence of autologous CD19-directed chimeric antigen receptor (CAR) T cells in patients with relapsed chronic lymphocytic leukemia (CLL) and B-cell acute lymphocytic leukemia (B-ALL). (ashpublications.org)
  • 2 While effective in lysing tumor cells in vitro, the clinical utility of these first-generation CAR-T cells was limited by their inability to sufficiently activate and sustain themselves in vivo. (ashpublications.org)
  • Schematic of the treatment of a patient with chimeric antigen receptor (CAR) T cells. (ashpublications.org)
  • 2) Transfection of T cells with a lentivirus containing genes for CAR directed against the tumor target antigen: binding of virus to T-cell membrane, fusion of virus with cell membrane, reverse transcription, DNA integration, and transcription/protein expression of CAR genes, and insertion of CAR into cell membrane. (ashpublications.org)
  • 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)
  • 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)
  • The immune system interacts closely with tumour cells via complex mechanisms and can result in either eradication of the tumour or immune evasion by the tumour (5). (cambridgemedicine.org)
  • Consequently, immune cells fail to recognise and kill tumour cells. (cambridgemedicine.org)
  • 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)
  • 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)
  • Recent data demonstrate that the recruitment of dendritic cells to neoplastic lesions (and hence the priming of tumor-specific CD8 + T cells) is highly dependent on radiotherapy dose and fractionation through a mechanism that involves the accumulation of double-stranded DNA in the cytoplasm of cancer cells and consequent type I IFN release. (aacrjournals.org)
  • The mixture with designed death-ligand 1 blockade resulted in potent healing efficiency which exhibited elevated tumor-infiltrating Compact disc8 T cells. (biotech2012.org)
  • 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)
  • Moreover, Compact disc70-T vaccination led to higher extension and migration of adoptively moved T cells into tumor sites and elicits improved healing results with peptide-based booster immu-nization. (biotech2012.org)
  • Bottom line These outcomes imply T cells endowed with Compact disc70 enable the look of effective vaccination strategies against solid tumor, which may conquer current restrictions of DC-based vaccines. (biotech2012.org)
  • 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)
  • 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)
  • O'Donnell showed that this is due to a strong early expansion, subsequent contraction, and establishment of memory response of tumor-specific CD8 + T cells. (acir.org)
  • The memory response originated with previously dysfunctional tumor-specific T cells and did not involve de novo priming. (acir.org)
  • In tumors, antigen-specific functional ICOS + CD4 + cells were increased, and both ICOS + CD4 + and CD8 + T cells were increased in the blood of patients. (acir.org)
  • Disease relapse following CAR T cell therapy can be categorized into two major patterns: target antigen loss relapse or antigen-positive relapse. (biomedcentral.com)
  • Antibodies to GITR have been shown to promote an anti-tumor response through loss of Treg lineage stability. (wikipedia.org)
  • 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)
  • 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)
  • In a clinical study of ACT published in 2011 , the treatment resulted in the disappearance of all tumors in 20/93 patients (21.5%) with advanced metastatic melanoma. (biopharmconsortium.com)
  • We show that treatment of the mice with a combination of anti-CTLA-4 + anti-PD1 mAbs results in partial clearance of the tumor with an improvement in survival. (unav.edu)
  • D, Survival curve represents tumor-free mice. (lyvgen.cn)
  • Survival was monitored daily, and tumors were measured twice per week until the animals died or the tumor volume reached the maximum allowed size. (polyplus-sartorius.com)
  • CD137 appears to be important for T cell proliferation and survival and induces monocyte activation. (adipogen.com)
  • It has become clear that hypoxia shapes and induces specific macrophage phenotypes that serve tumor malignancy, as hypoxia promotes immune evasion, angiogenesis, tumor cell survival, and metastatic dissemination. (nutriforce.cn)
  • This translated to reduced tumor growth and increased survival in mice. (acir.org)
  • B-RafV600E inhibitors have been suggested to promote tumor regression with the help of host immunity but this hypothesis has not been examined directly in detail. (cancer-pictures.org)
  • 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)
  • However, the addi-tion of either recombinant IL-2 or an anti-CD137 mAb markedly improves both outcomes in these mice. (unav.edu)
  • Mice that cleared the 200 mm3 tumors were rechallenged. (lyvgen.cn)
  • When tumors reached a volume of 80-100 mm3 (day 0) mice were randomized into different groups of treatment according to the experiment. (polyplus-sartorius.com)
  • Some degree of control of non-injected tumor lesions following BO-112 intratumoral treatment was found in mice bearing bilateral B16-OVA melanomas, an activity which was enhanced with co-treatment with systemic anti-CD137 and anti-PD-L1 mAbs. (polyplus-sartorius.com)
  • Nature communications 2022 - Prdm1 attenuates its effects on tumor growth inhibition through PD-L1-induced tumor immune evasion in immune-competent mice. (thermofisher.com)
  • a Representative subcutaneous tumors (left)/orthotopic transplantation tumors (right) collected from Hepa1-6-bearing C57BL/6 mice. (thermofisher.com)
  • b Tumor proliferation curves of subcutaneous xenografts in Hepa1-6-bearing C57BL/6 mice. (thermofisher.com)
  • Intratumoral treatment with BO-112 of subcutaneous tumors derived from MC38, 4 T1 and B16-F10 leads to remarkable local disease control dependent on type-1 interferon and gamma-interferon. (polyplus-sartorius.com)
  • CD137: When this molecule, also called 4-1BB, is bound by CD137 ligand, the result is T-cell proliferation. (wikipedia.org)
  • CusabioProtein Description: Extracellular DomainAlternative Name (s) : CD137;ILA;TNFRSF9;4-1BB ligand receptor;CDw137;T-cell antigen. (joplink.net)
  • Combining tumor-specific adoptive T cell therapy to the aCTLA-4/aPD1/rIL2 or aCTLA-4/aPD1/aCD137 reg-imens enhances efficacy in a synergistic manner. (unav.edu)
  • The data published in JITC describe the application of Bicycle's unique technology to produce a new class of potential immuno-oncology therapies: tumor-targeted immune cell agonists, or TICAs," said Nicholas Keen, Ph.D., Chief Scientific Officer of Bicycle Therapeutics. (svhealthinvestors.com)
  • CD137L is also expressed in carcinoma cell lines, and is thought to be involved in T cell-tumor cell interactions. (fishersci.com)
  • I. To assess for tumor-based biomarkers of response and resistance to this combination therapy using single-cell RNA sequencing (scRNA-seq) and high-dimensional flow cytometry. (bcan.org)
  • However, there are notable challenges with CAR T-cell therapy, including non-sustained responses, antigen escape, and life-threatening adverse effects. (cambridgemedicine.org)
  • 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)
  • 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)
  • Pre- and post-treatment tumor analysis after anti-CTLA-4 treatment demonstrated changes in a number of T cell genes, the most surprising of which was the ICOS pathway. (acir.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)
  • and BT7480, a Bicycle TICA™ targeting Nectin-4 and agonizing CD137, in company-sponsored Phase I/II trials. (onenucleus.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)
  • iii) The hypoxic tumor environment is immunosuppressive and prevents an antitumor response. (nutriforce.cn)
  • 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)
  • Upon mRNA intratumoral injections in the transplantable mouse cancer models CT26, MC38, and B16OVA, potent therapeutic effects were observed following repeated injections into the tumors. (unav.edu)
  • 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)
  • The role of tumor-associated macrophages (TAMs) in cancer is often correlated with poor prognosis, even though this statement should be interpreted with care, as the effects of macrophages primarily depend on their localization within the tumor. (nutriforce.cn)
  • Additionally, TAMs in the hypoxic niches within the tumor are known to mediate resistance to several anticancer treatments and to promote cancer relapse. (nutriforce.cn)
  • To assess the presence of antigen-specific immune responses to a broad panel of candidate tumor antigens. (bcan.org)
  • Taken together our results establish the critical role of immune-related changes with key contributions for CD40L and IFNγ signaling in the anti-tumor responses brought on in vivo by BRafV600E inhibitors. (cancer-pictures.org)
  • Additionally, induced co -expression of luciferase, EGFP, and the melanosomal antigen gp100 facilitates studies on the underlying immunological mechanisms. (unav.edu)
  • The combination of Take action with chemotherapy and bevacizumab caused 80% overall response, 26.7% complete response, and halted tumor progression in stage IV CRC patients (230). (azd1152.com)
  • Dr. Sharma's main takeaway was that analysis of tumor samples before and after treatment should enable rational guidance for therapeutic decisions. (acir.org)
  • Monoclonal anti-mouse Compact disc40 (FGK45.5) and anti-4.1BB/CD137 (2A) were prepared from hybridoma tradition supernatants. (biotech2012.org)
  • Tumor necrosis factor ligand superfamily: involvement in the pathology of malignant lymphomas. (bdbiosciences.com)
  • Glioblastoma (GB) is the most frequent malignant primary brain tumor in adults, without any curative treatment options available at present. (frontiersin.org)
  • Glioblastoma (GB) is the most common and aggressive primary brain tumor in adults and currently incurable. (frontiersin.org)
  • 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)