Similar Datasets
Project description:CD137 cis-costimulation is superior to trans-costimulation at inducing transcriptomic differences in T-cell proliferation and DNA repair programs We used microarrays to detail differentially expressed genes of cis- and trans CD137-costimulated CD8 T cells with respect to CD3-TCR stimulation
2021-09-28 | GSE158041 | GEO
Project description: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. CD137 agonists attain immunotherapeutic antitumor effects in cancer mouse models and multiple agents of this kind are undergoing clinical trials. We show that cIAP1 and cIAP2 are physically associated with the CD137-signaling complex. Moreover, cIAPs are required for CD137 signaling towards the NF-κB and MAPK pathways and for costimulation of human and mouse T lymphocytes. Functional evidence was substantiated with SMAC-mimetics that trigger cIAPs degradation and by transfecting cIAP dominant-negative variants. 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.
2024-05-24 | PXD042585 | Pride
Project description:The cell surface glycoprotein CD137, which is also known as 4-1BB, belongs to the group of co-stimulatory immune receptors and is a member of the TNF receptor superfamily (TNFRSF). It is preferentially found on activated T-cells and regulatory T-cells. In T-cells, CD137-crosslinking delivers a potent co-stimulatory signal as it promotes T-cell proliferation, formation of memory cells and enhances survival. Despite numerous studies investigating the effects of co-stimulatory CD137 in T-cells, little is known regarding the role of CD137 in human monocytes/macrophages. To investigate the effect of CD137 triggering on human monocytes, monocytes were isolated and treated with an agonistic CD137 mAb and subsequently analyzed by RNA-seq.
2021-06-17 | GSE171108 | GEO
Project description:We report the differences of gene expression pattern of tumor-infiltrating CD8 T cells between CD137 expressing cells and CD137 non-expressing cells in human metastatic ovarian cancer. Samples are obtained from 3 ovarian cancer patients, and we sorted CD137 expressing cells and CD137 non-expressing cells in CD39 expressing CD8 T cells for RNA sequencing. We found that even though the CD39 expression and PD-1 expression levels are similar, CD137 expressing cells showed more activated and less exhausted phenotypes than CD137 non-expressing cells.
2020-05-12 | GSE150301 | GEO
Project description:CD137 (4-1BB) is a member of the TNFR superfamily that represents a promising target for cancer immunotherapy. Recent insights into the function of TNFR agonist antibodies implicate epitope, affinity, and IgG subclass as critical features, and these observations help explain the limited activity and toxicity seen with clinically tested CD137 agonists. Here we describe the preclinical characterization of CTX-471, a fully human IgG4 agonist of CD137 that engages a unique epitope that is shared by human, cynomolgus monkey, and mouse and is associated with a differentiated pharmacology and toxicology profile. In vitro, CTX-471 increased IFN-γ production by human T cells in an FcγR-dependent manner, displaying an intermediate level of activity between two clinical-stage anti-CD137 antibodies. In mice, CTX-471 exhibited curative monotherapy activity in various syngeneic tumor models and showed a unique ability to cure mice of very large (~500 mm3) tumors compared to validated antibodies against checkpoints and TNFR superfamily members. Extremely high doses of CTX-471 were well-tolerated, with no signs of hepatic toxicity. Collectively, these data demonstrate that CTX-471 is a unique CD137 agonist that display an excellent safety profile and an unprecedented level of monotherapy efficacy against very large tumors.
2020-01-30 | GSE144473 | GEO