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EGFR-IL12-CART Cells for Patients With Metastatic Colorectal Cancer

ABSTRACT: This is a clinical study to observe the maximum tolerated dose (MTD) and the safety and feasibility of chimeric antigen receptor EGFR (EGFR -IL12 -CART) cells in metastatic patients with colorectal cancer.

DISEASE(S): Metastatic Colorectal Cancer,Colorectal Neoplasms

PROVIDER: 2274283 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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EGFR CART Cells for Patients With Metastatic Colorectal Cancer

Project description:This is a clinical study to observe the maximum tolerated dose (MTD) and the safety and feasibility of chimeric antigen receptor EGFR (EGFR CART) cells in metastatic patients with colorectal cancer.

| 2244323 | ecrin-mdr-crc

mRNA Profiling of Chronically Stimulated CART19-28z Cells in the Manuscript IL-4 Drives Exhaustion of CD8+ CART Cells

Project description:Durable response to chimeric antigen receptor T (CART) cell therapy remains limited in part due to CART cell exhaustion. Here, we investigate the regulation of CART cell exhaustion with three independent approaches including: a genome-wide CRISPR knockout screen using an in vitro model for exhaustion, RNA and ATAC sequencing on baseline and exhausted CART cells, and RNA and ATAC sequencing on pre-infusion CART cell products from responders and non-responders in the ZUMA-1 clinical trial. Each of these approaches identify interleukin (IL)-4 as a regulator of CART cell dysfunction. Further, IL-4-treated CD8+ CART cells develop signs of exhaustion independently of the presence of CD4+ CART cells. Conversely, IL-4 pathway editing or the combination of CART cells with an IL-4 monoclonal antibody improves antitumor efficacy and reduces signs of CART cell exhaustion in mantle cell lymphoma xenograft mouse models. Therefore, we identify both a role for IL-4 in inducing CART exhaustion and translatable approaches to improve CART cell therapy.

2024-08-01 | GSE273294 | GEO

ATAC Sequencing of Baseline and Chronically Stimulated CART19-28z Cells in the Manuscript IL-4 Drives Exhaustion of CD8+ CART Cells

2024-08-01 | GSE273297 | GEO

Genome-wide CRISPR Knockout Screen of Healthy Donor CART19-28ζ Cells in the Manuscript IL-4 Drives Exhaustion of CD8+ CART Cells

2024-08-01 | GSE273299 | GEO

Mutations and RNA-binding proteins controlling CD19 splicing and CART-19 therapy resistance: PTBP1 iCLIP2 in NALM-6 cells

Project description:We developed a massively parallel reporter assay to determine the splicing effects of all mutations in the region comprising CD19 exons 1-3. Despite the great success of CART-19 (chimeric antigen receptor-armed autologous T-cells) immunotherapy to treat B-cell acute lymphoblastic leukaemia (B-ALL), many patients relapse due to loss of the targeted CD19 epitope. Since epitope loss can be caused by CD19 exon 2 mis-splicing, we set out to learn the regulatory code that controls CD19 alternative splicing.

2022-06-05 | GSE182893 | GEO

Mutations and RNA-binding proteins controlling CD19 splicing and CART-19 therapy resistance: Minigene library RNA-seq

2022-06-05 | GSE182892 | GEO

Mutations and RNA-binding proteins controlling CD19 splicing and CART-19 therapy resistance: Minigene library DNA-seq

2022-06-05 | GSE182891 | GEO

GPR162 is a beta cell CART receptor [INS1_GPR162]

Project description:Cocaine and amphetamine-regulated transcript (CART) is expressed in pancreatic islet cells and neuronal elements. We have previously established insulinotropic actions of CART in human and rodent islets. The receptor for CART in the pancreatic beta cells is unidentified. We used RNA sequencing of Cartpt knock down (KD) INS-1 832/13 cells and identified GPR162 as the most Cartpt-regulated receptor. We therefore tested if GPR162 mediates the effects of CART in beta cells. Binding of CART to GPR162 was established using proximity ligation assay, radioactive binding and co-immunoprecipitation, and KD of Gpr162 mRNA caused reduced binding. Gpr162 KD cells had blunted CARTp-induced exocytosis, and reduced CARTp-induced insulin secretion. Furthermore, we identified a hitherto undescribed GPR162-dependent role of CART as a regulator of cytoskeletal arrangement. Thus, our findings provide mechanistic insight into the effect of CART on insulin secretion and show that GPR162 is the CART receptor in beta cells.

2023-10-20 | GSE245691 | GEO

GPR162 is a beta cell CART receptor [CART_KD]

2023-10-20 | GSE245796 | GEO

GD2-CART cells and iPSC-derived GD2-CART cells (scRNA-Seq)

Project description:We showed that iPSC-derived GD2-CART therapy for SCLC was more effective than peripheral blood-derived GD2-CART. Here, we investigated the molecular difference between iPSC-derived GD2-CARTs and peripheral blood-derived GD2-CARTs.

2023-10-25 | GSE245955 | GEO

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