Project description:Chimeric antigen receptor (CAR)-T cell therapy is a promising therapeutic approach for relapsed or refractory acute myeloid leukemia (AML). However, optimal target antigens have yet to be established. A subset of AML cells express TNF, which is initially expressed on the cell surface and subsequently secreted by proteolytic cleavage of the extracellular portion. We generated CAR-T cells targeting the N-terminal fragment of TNF (TNF-NTF) that remains on the cell surface after shedding. We ablated TNF gene to avoid fratricide and coexpressed chimeric cytokine receptor (G6/7R) that we had previously developed in CAR-T cells to provide constitutive IL-7 signaling. The G6/7R-expressing TNF-TNF CAR-T cells exhibited potent and durable therapeutic efficacy in vivo. Our data suggest that TNF-TNF may be a promising target antigen for CAR-T cells applicable to AML.
Project description:We performed transcriptome sequencing on Neo-2/15 stimulated CAR NK cells,to shed light on the function and phenotype changes of CAR-NK cells stimulated by IL-2 and Neo-2/15.
Project description:HMEC cultures were left untreated or stimulated for 5h with 2 ng/ml TNF. Comparison of the gene expression profiles revealed the TNF-mediated gene expression changes.
Project description:HUVEC were left untreated or stimulated for 5h with 2 ng/ml TNF. Comparsion of the gene profiles revealed TNF-mediated gene expression changes in HUVEC.
Project description:The series was designed to obtain gene expression patterns of TNF-alpha stimulated CaCo-2 cells. Keywords: TNF-alpha stimulation This series represents a group of 18 samples in 2 groups: 10 samples derived from not stimulated CaCo-2 cells, 8 samples from CaCo-2 cells stimulated with TNF-alpha in final concentration of 5 ng/ml for 60 min.
Project description:The series was designed to obtain gene expression patterns of TNF-alpha stimulated THP-1 cells. Keywords: TNF-alpha stimulation This series represents a group of 15 samples in two groups: 7 samples derived from not stimulated THP-1 cells, 8 from THP-1 cells stimulated with TNF-alpha in a final concentration of 5 ng/ml for 60 min.
Project description:The specific contribution of the two TNF-receptors Tnfr1 and Tnfr2 to TNF-induced inflammation in the glomerulus is unknown. In mice, TNF exposure induces glomerular expression of inflammatory mediators like adhesion molecules and chemokines in vivo, and glomerular accumulation of leukocytes. To examine Tnfr-specific inflammatory responses in intrinsic glomerular cells but not infiltrating leukocytes we performed microarray gene expression profiling on intact glomeruli isolated from wild-type and Tnfr-deficient mice following TNF exposure in vitro. Glomeruli were isolated from male C57BL/6J wild-type and Tnfr-deficient mice applying a magnetic bead-based isolation technique. Isolated intact glomeruli were stimulated with TNF for 12 hours in vitro for subsequent RNA extraction and hybridization on Affymetrix microarrays.
Project description:To understand the molecular determinants of CAR-T cell polyfunctionality, we simultaneously measured the protein and RNA expression levels of 23 single CD8+ D4-IgG4H-CD28TM CAR T cells targeting GPC1 stimulated with T3M4 pancreatic cancer cells. We identified two CAR-T clusters, low polyfunctionality and high polyfunctionality subsets, in a 2D t-SNE plot. Moreover, our single-cell mRNA expression profiling revealed 23 genes that displayed statistically significant, concordant differences between the two cell subsets.