Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

FcγRIIB engagement drives agonistic activity of Fc-engineered αOX40 antibody to stimulate human tumor-infiltrating T cells

ABSTRACT: FcγRIIB engagement drives agonistic activity of Fc-engineered αOX40 antibody to stimulate human tumor-infiltrating T cells

PROVIDER: PRJNA640811 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR12060531_1.fastq.gz	Fastqsanger.gz
	SRR12060531_2.fastq.gz	Fastqsanger.gz
	SRR12060532_1.fastq.gz	Fastqsanger.gz
	SRR12060532_2.fastq.gz	Fastqsanger.gz
	SRR12060533_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 36

Similar Datasets

FcγRIIB engagement drives agonistic activity of Fc-engineered αOX40 antibody to stimulate human tumor-infiltrating T cells

Project description:Background: OX40 (CD134) is a co-stimulatory molecule of the tumor necrosis factor receptor (TNFR) superfamily, that is currently investigated as a target for cancer immunotherapy. However, despite promising results in murine tumor models, the clinical efficacy of agonistic αOX40 antibodies in treatment of cancer patients has fallen short of the high expectation in earlier stage trials. Methods: Using lymphocytes from resected tumor, tumor-free tissue and PBMC of 4 hepatocellular and colorectal cancer patients, we performed RNA-Seq to evaluate OX40-mediated transcriptional changes in CD4+ and CD8+ human tumor-infiltrating lymphocytes (TILs). Results: The transcriptional landscape of CD4+ and CD8+ TILs shifted towards a pro-survival, inflammatory and chemotactic profile upon treatment with αOX40_v12.

2020-06-22 | GSE152904 | GEO

Fc?RIIB engagement drives agonistic activity of Fc-engineered ?OX40 antibody to stimulate human tumor-infiltrating T cells.

Project description:BACKGROUND:OX40 (CD134) is a costimulatory molecule of the tumor necrosis factor receptor superfamily that is currently being investigated as a target for cancer immunotherapy. However, despite promising results in murine tumor models, the clinical efficacy of agonistic ?OX40 antibodies in the treatment of patients with cancer has fallen short of the high expectation in earlier-stage trials. METHODS:Using lymphocytes from resected tumor, tumor-free (TF) tissue and peripheral blood mononuclear cells (PBMC) of 96 patients with hepatocellular and colorectal cancers, we determined OX40 expression and the in vitro T-cell agonistic activity of OX40-targeting compounds. RNA-Seq was used to evaluate OX40-mediated transcriptional changes in CD4+ and CD8+ human tumor-infiltrating lymphocytes (TILs). RESULTS:Here, we show that OX40 was overexpressed on tumor-infiltrating CD4+ T cells compared with blood and TF tissue-derived T cells. In contrast to a clinical candidate ?OX40 antibody, treatment with an Fc-engineered ?OX40 antibody (?OX40_v12) with selectively enhanced Fc?RIIB affinity, stimulated in vitro CD4+ and CD8+ TIL expansion, as well as cytokine and chemokine secretions. The activity of ?OX40_v12 was dependent on Fc?RIIB engagement and intrinsic CD3/CD28 signals. The transcriptional landscape of CD4+ and CD8+ TILs shifted toward a prosurvival, inflammatory and chemotactic profile on treatment with ?OX40_v12. CONCLUSIONS:OX40 is overexpressed on CD4+ TILs and thus represents a promising target for immunotherapy. Targeting OX40 with currently used agonistic antibodies may be inefficient due to lack of OX40 multimerization. Thus, Fc engineering is a powerful tool in enhancing the agonistic activity of ?OX40 antibody and may shape the future design of antibody-mediated ?OX40 immunotherapy.

| S-EPMC7478034 | biostudies-literature

The effect of a novel form of macrophage colony-stimulating factor (CSF1-Fc) on gene expression in the liver.

Project description:Treatment of mice with daily injections of CSF1-Fc produce a 50% increase in the size of the liver within 5 days. There was extensive proliferation of hepatocytes, similar to that seen following partial hepatectomy. Comparative gene expression profiles of the treated and control livers, alongside macrophages grown in CSF1, indicate extensive infiltration by macrophages in response to CSF1-Fc, and demonstrate that infiltrating macrophages produced several candidate mediators of hepatocyte proliferation.

2013-12-31 | E-GEOD-52636 | biostudies-arrayexpress

Geitlerinema sp. FC II strain:FC II

Project description:Geitlerinema sp. FC II strain:FC II Genome sequencing and assembly

| PRJNA399071 | ENA

Transcriptomic analysis of 4NQO-induced oral squamous cell carcinoma with agonistic anti-CD40 treatment

Project description:To investigate the anti-tumor effect of agonistic anti-CD40, 4NQO-indued OSCC mice with agonistic anti-CD40.

2023-10-23 | GSE217407 | GEO

Mapping of nascent RNA in MLL2 F/F and FC/FC MEF cells

Project description:Global Run-On has been performed in MLL2 F/F and FC/FC MEF cells. The aim of the experiment is to test how the lack of MLL2 affects nascent RNA transcription. Four samples were analyzed - 2 independent replicates. The experiments were performed using immortalized mouse embryonic fibroblasts (MEF) in which both MLL2 alleles were targeted by the loxp system (F/F cells). Tamoxifen treatment of the F/F cells for 24 hours results in the excision of both MLL2 alleles (FC/FC cells).

2016-04-13 | E-GEOD-73126 | biostudies-arrayexpress

Neutralizing antibodies against SARS-CoV-2 require intact Fc effector functions and monocytes for optimal therapeutic activity

Project description:SARS-CoV-2 has spread globally and caused the COVID-19 pandemic. Although passively delivered neutralizing antibodies against SARS-CoV-2 are in clinical trials, their mechanism of action in vivo is incompletely understood. Here, we define correlates of protection of neutralizing human monoclonal antibodies (mAbs) in SARS-CoV-2-infected mice. Whereas Fc effector functions are fully dispensable when mAbs are administered as prophylaxis, they are required for optimal protection as therapy. When given after infection, intact but not LALA-PG loss of Fc effector function variant mAbs reduce SARS-CoV-2 burden and lung disease in mice and hamsters. Fc engagement of neutralizing antibodies mitigates inflammation and improves respiratory mechanics, and transcriptional profiling suggests these phenotypes are associated with diminished innate immune signaling and enhanced tissue repair. Immune cell depletions establish that neutralizing mAbs require monocytes for therapeutic efficacy. Our study demonstrates that therapeutic neutralizing mAbs require Fc effector functions to reduce SARS-CoV-2 infection and modulate protective immune responses.

2021-03-01 | GSE161615 | GEO

Mapping of nascent RNA in MLL2 F/F and FC/FC MEF cells

Project description:Global Run-On has been performed in MLL2 F/F and FC/FC MEF cells. The aim of the experiment is to test how the lack of MLL2 affects nascent RNA transcription.

2016-04-13 | GSE73126 | GEO

Fc-mediated effector function contributes to the in vivo antiviral effect of an HIV broadly neutralizing antibody.

Project description:Treatment of HIV infection with either anti-retroviral therapy (ART) or neutralizing monoclonal antibodies (NAbs) leads to a reduction in HIV plasma virus. Both ART and NAbs prevent new rounds of viral infection but NAbs may have the additional capacity to accelerate the loss of virus-infected cells through Fc gamma receptor (FcgR) mediated effector functions, which should affect the kinetics of plasma virus decline. Here we formally test this premise in vivo by comparing the plasma virus response to a single dose treatment with either unmodified NAb or those with either reduced or augmented Fc function. When infused into viremic SHIV-infected rhesus macaques, there was a 21% difference in slope of plasma virus decline between wt NAb and NAb with reduced Fc function. NAb engineered to increase FcgRIII binding and improve ADCC in vitro resulted in arming of effector cells in vivo yet led to viral decay kinetics similar to NAbs with reduced Fc function. These studies show that the predominant mechanism of antiviral activity of HIV NAbs is through inhibition of viral entry, but that Fc function does contribute to the overall antiviral activity, making them unique from standard ART. However, these data also show that increased FcgRIII engagement is insufficient to improve in vivo virus clearance.

2020-07-20 | GSE136938 | GEO

Escherichia coli isolate:FC

Project description:Escherichia coli isolate:FC Genome sequencing

| PRJNA668647 | ENA