Clinical study on the safety and effectiveness of CART cells in the treatment of advanced refractory GUCY2C-positive advanced colorectal cancer
Ontology highlight
ABSTRACT:
DISEASE(S): Late Colorectal Cancer
PROVIDER: 36236 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
Similar Datasets
Project description:Interventions: Prevention Group:Take Regofini;Controlled Group:Take other anti-tumor drugs
Primary outcome(s): Proportion of patients who achieved complete remission (CR) at the 8th week and partial remission (PR) at any time and stable disease (SD) at any time.;Partial response;complete response
Study Design: Parallel
| 89141 | ecrin-mdr-crc
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
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
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 | GSE245796 | GEO
Project description:In this study, 58 r/r DLBCL patients treated with tandem CD19/CD20 CAR T cells. Twenty-seven patients had durational responses for more than 24 months, and the median PFS was 21.7 months. But 15 patients still did not have an objective response, and 11 patients relapsed within 1 year. The analysis found that CD8+TSCM cells with higher frequency and stronger activation ability in CART products were the key to achieving clinical sustained objective response. Bulk-RNA-seq results confirmed that CD8+CART cells in CR group had higher expression of memory-related genes and transcription factors and lower expression of activation/depletion related genes than those in PD patients. Naive CD8 cells also showed similar differential expression in apheresis. The use of Naive cells as the source cell population for CART preparation could partially improve CART function, but could not completely reverse it. It is suggested that the resistance of DLBCL to tandem CD19/CD20 CAR T cell therapy may be caused by the decreased function and the loss of expression of memory genes of the source Naive T cells.
2023-11-09 | GSE223655 | GEO
Project description:GD2-CART cells and iPSC-derived GD2-CART cells (scRNA-Seq)
| PRJNA1030434 | ENA
Project description:The aim of our study was to evaluate the ability of miRNA expression patterns to predict chemotherapy response in a cohort of 39 patients with metastatic colorectal carcinoma To define miRNA signature, samples were obtained from tumor tissue samples of 39 patients . Patients were divided into responders or non-responders according to tresponse treatment with a chemotherapy regimen that included fluoropyrimidines and either oxaliplatin or irinotecan .Tumor response was evaluated by conventional methods according to the standard RECIST 1.0 criteria: a complete response (CR) was defined as the disappearance of all measurable and evaluable evidence of disease; a partial response (PR) was defined as a > 30% decrease in the sum of the longest diameters of target lesions; stable disease (SD) was considered if the tumor burden decreased less than 30% or increased less than 20%; and progressive disease (PD) was indicated by a >20% increase in the sum of the longest diameters of target lesions or the appearance of any new lesion. Patients were classified according to best response to chemotherapy in two groups: those that achieved an objective response (Responders [R]: CR + PR) and those that did not (Non-responders [NR]: SD + PD). Mature human miRNA expression was detected and quantified using the TaqMan® Low Density Arrays (TLDA). The Human MicroRNA Card Set v2.0 array is a two card set containing a total of 384 TaqMan® MicroRNA Assays per card to enable accurate quantification of 667 human microRNAs, all catalogued in the miRBase database. Expression of target miRNAs was normalized in relation to the expression of MammU6. Cycle threshold (Ct) values were calculated using the SDS software v.2.3 using automatic baseline settings and a threshold of 0.2. Relative quantification of miRNA expression was calculated by the 2−ΔCt method (Applied Biosystems user bulletin no. 2 (P/N 4303859)).
2014-08-12 | E-GEOD-48664 | biostudies-arrayexpress
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
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 | GSE273297 | GEO
Project description:cART Treated monocyte derived macrophages
| PRJNA801872 | ENA