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A multimodal assay identifies optimized binders for a bicistronic CAR against GPC2 OR CD276 to overcome heterogeneity in Neuroblastoma

ABSTRACT: A multimodal assay identifies optimized binders for a bicistronic CAR against GPC2 OR CD276 to overcome heterogeneity in Neuroblastoma

PROVIDER: PRJNA752052 | ENA |

REPOSITORIES: ENA

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A multimodal assay identifies optimized binders for a bicistronic CAR against GPC2 OR CD276 to overcome heterogeneity in Neuroblastoma

Project description:Neuroblastoma (NB) is the most common extra-cranial solid tumor in children and remains deadly in patients with high-risk disease. Single chimeric antigen receptor T-cell therapies (CAR-T) for solid tumor have shown poor efficacy in clinical trials due, in part, to T cell exhaustion and uneven expression of target antigens in tumors. Here, we attempted to target Glypican-2(GPC2) and CD276(B7-H3), both highly but heterogeneously expressed on NB cell surface, to overcome these challenges in single CAR T- therapies. First, to identify optimal binders for CAR T- cell targeting each antigen, we made individual CAR constructs using multiple binders against these antigens and utilized a multimodal approach including simultaneous protein and transcriptome measurement at single cell level to characterize each individual CAR T- cell in a pooled strategy. Combined with cell expansion and cytotoxicity assays, we identified the most effective CAR construct for each target.

2022-03-18 | GSE181437 | GEO

RNA-seq analysis of CD276-high/EpCAM+ cells from HNSCC patient-derived-xenograft

Project description:We performed RNA sequencing (RNA-seq) to compare the gene expression pattern between CD276-high/EpCAM+ and CD276-low/EpCAM+ cells isolated from human HNSCC PDX. We identified a cohort of key oncogenes associate with cancer stemness enriched in CD276-high cells. Suggesting CD276 may play a positive role in maintaining cancer stem cells in human head and neck squamous cell carcinoma.

2021-05-28 | GSE132627 | GEO

CD276 is an important player in macrophage recruitment into the tumor and an upstream regulator for PAI-1

Project description:70-100% of colorectal, prostate, ovarian, pancreatic and breast cancer specimens show expression of CD276 (B7-H3), a potential immune checkpoint family member. Several studies have shown that high CD276 expression in cancer cells correlates with a poor clinical prognosis. This has been associated with the presence of lower tumor infiltrating leukocytes. Among those, tumor-associated macrophages can comprise up to 50% of the tumor mass and are thought to support tumor growth through various mechanisms. However, a lack of information on CD276 function and interaction partner(s) impedes rigorous evaluation of CD276 as a therapeutic target in oncology. Therefore, we aimed to understand the relevance of CD276 in tumor-macrophage interaction by employing a 3D spheroid coculture system with human cells. Our data show a role for tumor-expressed CD276 on the macrophage recruitment into the tumor spheroid, and also in regulation of the extracellular matrix modulator PAI-1. Furthermore, our experiments focusing on macrophage-expressed CD276 suggest that the antibody-dependent CD276 engagement triggers predominantly inhibitory signaling networks in human macrophages.

2021-07-28 | GSE165610 | GEO

Multimodal chromatin profiling using nanobody-based single-cell CUT&Tag

Project description:Probing epigenomic marks such as histone modifications at a single cell level in thousands of cells has been recently enabled by technologies such as scCUT&Tag. Here we developed a multimodal and optimized iteration of scCUT&Tag called nano-CT (for nano-CUT&Tag) that allows simultaneous probing of three epigenomic modalities at single-cell resolution, using nanobody-Tn5 fusion proteins. nano-CT is compatible with starting materials as low as 25 000 cells and has significantly higher resolution than scCUT&Tag, with a 16-fold increase in the number of fragments per cells. We used nano-CT to simultaneously profile chromatin accessibility, H3K27ac and H3K27me3 in a complex tissue - juvenile mouse brain. The obtained multimodal dataset allowed for discrimination of more cell types/states that scCUT&Tag, and inference of chromatin velocity between ATAC and H3K27ac in the oligodendrocyte (OL) lineage. In addition, we used nano-CT to deconvolute H3K27me3 repressive states and infer two sequential waves of H3K27me3 repression at distinct gene modules during OL lineage progression. Thus, given its high resolution, versatility, and multimodal features, nano-CT allows unique insights in epigenetic landscapes in different biological systems at single cell level.

2022-09-20 | GSE198467 | GEO

Single-cell Sequencing Analysis Identifies Intratumoral Cell Population in Head and Neck Squamous Cell Carcinoma from 4NQO-induced Mice upon anti-CD276 Therapy

Project description:In this study, we aimed to identifies the landscape alterations of intratumoral cell population in HNSCC from 4NQO-induced mice upon anti-CD276 treatment by using single cell sequencing analysis.we characterized the alterations of intratumoral cell population by separating cancer cells and yielded 6 distinct cancer cell subpopulations defined by the transcriptional state of cells and known marker genes, including the sunpopulation with pEMT, stress, typical epithelial differentiation, high cell-cycling, metabolism and immune fetures. In response of CD276 treatment, the frequecey of cells with pEMT, cell cycling and immune features are dcreased as compared to the vehicle control mice.

2021-05-28 | GSE164817 | GEO

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Project description:The simultaneous measurement of multiple modalities, known as multimodal analysis, represents an exciting frontier for single-cell genomics and necessitates new computational methods that can define cellular states based on multiple data types. Here, we introduce ‘weighted-nearest neighbor’ analysis, an unsupervised framework to learn the relative utility of each data type in each cell, enabling an integrative analysis of multiple modalities. We apply our procedure to a CITE-seq dataset of hundreds of thousands of human white blood cells alongside a panel of 228 antibodies to construct a multimodal reference atlas of the circulating immune system. We demonstrate that integrative analysis substantially improves our ability to resolve cell states and validate the presence of previously unreported lymphoid subpopulations. Moreover, we demonstrate how to leverage this reference to rapidly map new datasets, and to interpret immune responses to vaccination and COVID-19. Our approach represents a broadly applicable strategy to analyze single-cell multimodal datasets, including paired measurements of RNA and chromatin state, and to look beyond the transcriptome towards a unified and multimodal definition of cellular identity.

2021-01-15 | GSE164378 | GEO

RNA sequencing analysis for mouse ovarian cancer cells and tumors response to B7-H3 (Cd276) depletion

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2022-01-10 | GSE174137 | GEO

Phase I exploratory clinical study of CD276-targeted chimeric antigen receptor T cells for the treatment of solid tumors

Project description:Interventions: experimental group:CD276-targeted chimeric antigen receptor T cells Primary outcome(s): SAE rate Study Design: Single arm

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Integrated analysis of multimodal single-cell data

Project description:Integrated analysis of multimodal single-cell data

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Single-cell multiome sequencing of human kidney anatomical regions with SHARE-seq

Project description:We developed an optimized, low-cost, split-pool barcoding-based multimodal profiling protocol based upon SHARE-seq (concurrent single-cell ATAC/RNA-seq). With SHARE-seq, we profiled human kidney samples from multiple different anatomical regions. Therefore, we develop a large-scale multimodal single-cell atlas for 3D anatomy of the human kidney.

2024-02-15 | GSE234788 | GEO

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