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Single-cell RNA sequencing of human IL-18R supported CAR T cells targeting oncofetal Tenascin C

ABSTRACT: Single-cell RNA sequencing of human IL-18R supported CAR T cells targeting oncofetal Tenascin C

PROVIDER: PRJNA1186711 | ENA |

REPOSITORIES: ENA

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Single-cell RNA sequencing of human IL-18R supported CAR T cells targeting oncofetal Tenascin C

Project description:C.TNC-CAR.Zip18R CAR-T cell of 2 donors were used for 2 in vitro experiments. In the first experiment, we did scRNA-seq for activated CAR-T cells. In the second experiment, the CAR-T cells of each donor were cocultured with tumor cells for 12 hrs, 24 hrs and 48 hrs. The CAR-T cells for each timepoints were extracted for scRNA-seq. Multiplexed 10x Genomics scRNA-seq were performed with a hashtag to label each sample.

2024-11-20 | GSE282046 | GEO

IL-18R supported CAR T cells targeting oncofetal tenascin C for the immunotherapy of pediatric sarcoma and brain tumors.

Project description:BackgroundOncofetal splice variants of extracellular matrix (ECM) proteins present a unique group of target antigens for the immunotherapy of pediatric cancers. However, limited data is available if these splice variants can be targeted with T cells expressing chimeric antigen receptors (CARs).MethodsTo determine the expression of the oncofetal version of tenascin C (TNC) encoding the C domain (C.TNC) in pediatric brain and solid tumors, we used quantitative reverse transcription PCR and immunohistochemistry. Genetically modified T cells were generated from human peripheral blood mononuclear cells and evaluated in vitro and in vivo.ResultsWe demonstrate that C.TNC is expressed on a protein level in pediatric tumors, including diffuse intrinsic pontine glioma, osteosarcoma, rhabdomyosarcoma, and Ewing sarcoma. We generate C.TNC-CAR T cells and establish that these recognize and kill C.TNC-positive tumor cells. However, their antitumor activity in vivo is limited. To improve the effector function of C.TNC-CAR T cells, we design a leucine zipper-based chimeric cytokine receptor that activates interleukin-18 signaling pathways (Zip18R). Expression of Zip18R in C.TNC-CAR T cells improves their ability to secrete cytokines and expand in repeat stimulation assays. C.TNC-CAR.Zip18R T cells also have significantly greater antitumor activity in vivo compared with unmodified C.TNC-CAR T cells.ConclusionsOur study identifies the C domain of the ECM protein TNC as a promising CAR T-cell therapy for pediatric solid tumors and brain tumors. While we focus here on pediatric cancer, our work has relevance to a broad range of adult cancers that express C.TNC.

| S-EPMC11580246 | biostudies-literature

Comparison of tenascin-C proficient versus tenascin-C deficient Mouse Embryonic Fibroblasts (MEFs)

2011-02-22 | GSE23547 | GEO

car

Project description:Drosophila melanogaster car, carnation, is differentially expressed in 11 experiment(s);

| FBgn0000257 | ExpressionAtlas

car

Project description:Drosophila melanogaster car, carnation, is expressed in 4 baseline experiment(s);

| FBgn0000257 | ExpressionAtlas

Comparison of tenascin-C proficient versus tenascin-C deficient Mouse Embryonic Fibroblasts (MEFs)

Project description:In order to investigate what signalling pathways are turned on by tenascin-C, we generated Mouse Embryonic Fibroblasts (MEFs) deficient for tenascin-C and compared their gene expression profile to MEFs proficient for tenascin-C. TNC-KO MEFs as well as WT MEFs in which tenascin-C was knocked-down (following stable transfection of a short hairpin RNA) were compared to WT MEFs (expressing strong endogenous levels of tenascin-C).

2011-02-22 | E-GEOD-23547 | biostudies-arrayexpress

Oncofetal reprogramming of the tumor vasculature

Project description:Oncofetal reprogramming of the tumor vasculature

| PRJNA1027431 | ENA

AP-MS with VAR2CSA and oncofetal chondroitin sulfate antibodies

Project description:Tumors display oncofetal chondroitin sulfate (ofCS) glycosaminoglycans that support disease progression and dissemination. ofCS can be detected by the the Plasmodium falciparum derived VAR2CSA protein but the development of recombinant VAR2CSA as a clinical tool has proven challenging. Here, we performed AP-MS experiments with newly developed antibodies with ofCS specificity comparable to VAR2CSA, as well as recombinant VAR2CSA bait.

2024-08-31 | PXD044455 | Pride

Human Rheumatoid Arthritis Synovial Fibroblasts: Control vs. Tenascin-C Stimulated

Project description:Transcriptional profiling of human rheumatoid arthritis synovial fibroblasts comparing control cells treated with BSA with cells treated with Tenascin-C.

2012-03-27 | GSE36757 | GEO

Oncofetal reprogramming of the tumor vasculature

Project description:Certain embryonic genes, such as carcinoembryonic antigens (CEA) and oncofetal antigens, become re-expressed in malignant transformation and we hypothesized that a similar phenomenon features tumor endothelial cells as well. Therefore, we performed a systematic search for mouse embryo-specific gene expression at days E11 and E18 in comparison to adult mouse and queried for overexpression of these genes in sorted murine tumor endothelial cells.

2025-04-09 | GSE245218 | GEO

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