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TN/SCM pre-selection generates CAR T-cell products driving superior anti-tumor responses while curtailing severe CRS

ABSTRACT: TN/SCM pre-selection generates CAR T-cell products driving superior anti-tumor responses while curtailing severe CRS

PROVIDER: PRJNA825749 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18731084.fastq.gz	Fastqsanger.gz
	SRR18731085.fastq.gz	Fastqsanger.gz
	SRR18731086.fastq.gz	Fastqsanger.gz
	SRR18731087.fastq.gz	Fastqsanger.gz
	SRR18731088.fastq.gz	Fastqsanger.gz

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TN/SCM pre-selection generates CAR T-cell products driving superior anti-tumor responses while curtailing severe CRS

Project description:Chimeric antigen receptor (CAR) T-cell expansion and persistence represent key factors to achieve complete responses and prevent relapses. These features are typical of early memory T cells, which can be highly enriched through optimized manufacturing protocols. Here, we investigated the efficacy and safety profiles of CAR T-cell products generated from pre-selected naive/stem memory T cells (TN/SCM), as compared to unselected T cells (TBULK). Notwithstanding their reduced effector signature in vitro, limiting CAR TN/SCM doses showed superior antitumor activity and the unique ability to counteract leukemia re-challenge in hematopoietic stem/precursor cell-humanized mice, featuring increased expansion rates and persistence, together with an ameliorated exhaustion and memory phenotype. Most relevantly, CAR TN/SCM proved to be intrinsically less prone to induce severe cytokine release syndrome, independently of the costimulatory endodomain employed. This safer profile was associated with milder T-cell activation, which translated in reduced monocyte activation and cytokine release. These data suggest that CAR TN/SCM are endowed with a wider therapeutic index compared to CAR TBULK.

2022-05-17 | GSE200661 | GEO

EXoO-Tn: Tag-n-Map the Tn Antigen in the Human Proteome

Project description:Tn antigen (Tn), a single N-acetylgalactosamine (GalNAc) monosaccharide attached to protein Ser and Thr residues, is found on most solid tumors yet rarely detected in adult tissues: featuring it one of the most distinctive signatures of cancers. Although it is prevalent in cancers, Tn-glycosylation sites are not entirely clear owing to the lack of suitable technology. Knowing the Tn-glycosylation sites will spur the development of the new vaccines, diagnostics, and therapeutics of cancers. Here, we report a novel technology named EXoO-Tn for large-scale mapping of Tn-glycosylation sites. EXoO-Tn utilizes glycosyltransferase C1GalT1 and isotopically-labeled UDP-Gal(13C6) to tag and convert Tn to Gal(13C6)-Tn. This exquisite Gal(13C6)-Tn structure is recognized by a human-gut-bacterial enzyme, called OpeRATOR, that specifically cleaves N-termini of the Gal(13C6)-Tn-occupied Ser and Thr residues to yield site-containing glycopeptides. The enzymes C1GalT1 and OpeRATOR could be used concurrently in one-pot. The effectiveness of EXoO-Tn was evaluated by analyzing Jurkat cells, where 947 Tn-glycosylation sites from 480 glycoproteins were mapped. Bioinformatic analysis of the identified site-specific Tn-glycoproteins revealed conserved motif, cellular localization, relative position in proteins, and mapped site-specific Tn-glycoproteome in different studies. Given the significance of Tn in cancers, EXoO-Tn is anticipated to have broad utilities in clinical study of cancers.

2022-02-15 | PXD014390 | Pride

Tissue Eosinophilia is Effective for Studying Differential Expression of Genes by RNA sequencing, and may offer Superior Insights into Chronic Rhinosinusitis than Study by Polyp Status

Project description:RNA sequencing (RNAseq) is being used to study inflammatory pathways in chronic rhinosinusitis (CRS). Our goal was to probe validity of tissue eosinophilia as a metric to study RNAseq in CRS. The study was conducted on prospectively enrolled subjects undergoing sinonasal surgery. Subjects were categorized as control, CRS, CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). CRS was also categorized by tissue eosinophil levels per high power field (EOS/HPF) as <10 EOS/HPF or ≥10 EOS/HPF. Ethmoidal tissue samples were processed, differentially expressed (DE) genes were calculated and Ingenuity pathway analysis (IPA) performed.Controls separated clearly from CRS by both study criteria (polyp status, EOS/HPF). In both analyses, CRS differentiated into two distinct CRS subgroups. However, heatmaps showed greater homogeneity within each CRS subtype when studied by eosinophilia versus polyp status. Overall, high differential gene expression was found in CRS versus controls, with 736 statistically significant differentially expressed (DE) genes. On comparison between between CRSwNP and CRSsNP, 60 DE genes were found and on analyzing by tissue EOS/HPF, 110DE genes were statistically significant between CRS <10 EOS/HPF and CRS ≥10 EOS/HPF analyses. Tissue eosinophilia as a metric was further validated by finding of IL 17 signalling pathway between <10EOS/HPF (increased) versus ≥10 EOS/HPF samples on pathway analysis. As a metric, tissue eosinophilia is at least as effective as analysis by polyp status for RNA sequencing and may potentially offer superior insights into mechanistic pathways.

2022-03-21 | GSE198950 | GEO

Light dependent gene expression in D. shibae wildtype compared to the gene expression in the transposonmutants D. shibae Dshi_1135::Tn, D. shibae ppaA::Tn and D. shibae ppsR::Tn

Project description:Light dependent gene expression in D. shibae wildtype compared to the gene expression in the transposonmutants D. shibae Dshi_1135::Tn, D. shibae ppaA::Tn and D. shibae ppsR::Tn. Dinoroseobacter shibae DFL12T (DSM 16493T) and the transposonmutants D. shibae Dshi_1135::Tn, D. shibae ppaA::Tn and D. shibae ppsR::Tn were grown in artificial saltwater minimal medium (SWM) in baffled flasks shaking at 180 rpm and 30 °C and incubation was performed under light, dark and bluelight conditions. D. shibae wild type and mutant strain were grown under aerobic conditions up to the mid exponential growth phase (OD578 nM 0.5).

2023-10-01 | GSE244289 | GEO

Gene expression profile of CD22 CAR T-cell products

Project description:Cytokine release syndrome (CRS) is a strong immune system response that can occur as a result of the reaction of a cellular immunotherapy with malignant cells. While the frequency and management of CRS in CAR T-cell therapy has been well documented, there is emerging interest in pre-emptive treatment to reduce CRS severity and improve overall outcomes. Accordingly, identification of genomic determinants that contribute to cytokine release may lead to the development of targeted therapies to prevent or abrogate the severity of CRS. We examined CD22 CAR T-cells using the Nanostring nCounter platform and found that the expression of the PFKFB4 gene and glycolytic pathway activity were upregulated in CAR T-cells in those who developed CRS compared to those who did not have CRS.

2022-08-03 | GSE200296 | GEO

TN removal

Project description:TN removal Raw sequence reads

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Label-free quantitative crotonylproteomics of mouse ovaries-Chronic resistant stress (CRS) and control group, two repeats each

Project description:We found that in Chronic Resistant Stress (CRS)-treated mice, the fertility and oocyte quality significantly decreased, and plenty of biochemical indexes significantly changed, so we guessed that the overall physical health of CRS mice was severely impacted. As one major strategy to investigate the mechanism how CRS impact the physical health, We chose label-free quantitative ovarian crotonylproteomics service from Hangzhou PTM Bio Co. We sent two repeats of two-month-old CRS CD1/ICR mouse ovaries and two repeats of control ovaries for characterization of differentially crotonylated proteins. Each repeat contained about 60 ovaries from 30 female mice, about 300 mg. Gross protein levels were also examined and used to normalize the protein crotonylation level.

2024-05-22 | PXD028961 | Pride

Tn-Seq of Benzalkonium Chloride Treated and Untreated Acinetobacter baumannii

Project description:The goal of this Tn-Seq study was to determine important determinants of Acinetobacter baumannii tolerance of sub-MIC concentrations of benzalkonium chloride. This Tn-seq data was then utilized to aide in the determination of the sub-MIC mechanism of action for benzalkonium chloride.

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Observation of the effects of the product Tn on the expression of A. thaliana genes - Project TN 2014: effect on Arabidopsis thaliana

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2017-02-01 | GSE93095 | GEO

Comparison of mRNA expression between naive CD4+ T (TN) cells treated or not treated with IL-1b

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