Project description:Persistence of infused antitumor T cells is one of the essential factors for durable therapeutic response. T cells undergo genome-wide alterations in epigenetic architecture upon repeated antigen encounter, which is inevitably accompanied by progressive T cell differentiation and loss of longevity. In this study, we explored key epigenetic factors associated with terminal T cell differentiation using CRISPR/Cas9-mediated knockout of epigenetic genes in chimeric antigen receptor (CAR)-engineered human T cells and identified PRDM1 as one of the key epigenetic genes regulating T cell differentiation. We compared epigenetic profiles of control and PRDM1-knockout CAR-T cells by ATAC-sequencing analysis.
Project description:Persistence of infused antitumor T cells is one of the essential factors for durable therapeutic response. T cells undergo genome-wide alterations in epigenetic architecture upon repeated antigen encounter, which is inevitably accompanied by progressive T cell differentiation and loss of longevity. In this study, we explored key epigenetic factors associated with terminal T cell differentiation using CRISPR/Cas9-mediated knockout of epigenetic genes in chimeric antigen receptor (CAR)-engineered human T cells and identified multiple key epigenetic genes. We analyzed gene expression profiles of CAR-T cells that were knocked out with the specific epigenetic genes by RNA-sequencing.
Project description:Interventions: experimental group:CD276-targeted chimeric antigen receptor T cells
Primary outcome(s): SAE rate
Study Design: Single arm
Project description:This clinical trial is an open-label, single-centre, dose escalation, phase I study designed to investigate the safety and tolerability of Haploidentical / Allogeneic NKG2DL-targeting Chimeric Antigen Receptor-grafted Gamma Delta (γδ) T Cells (CTM-N2D) in Subjects with Relapsed or Refractory Solid Tumour. The study objectives of this phase I study are to determine the safety, activity and the safe dose of haploidentical or allogeneic NKG2DL-targeting chimeric antigen receptor-grafted γδ T cells given four times weekly in patients with relapsed or refractory solid tumors of different types.
Project description:In this data set we include expression data from human CD4+ T cells isolated on day 0, 6, 11 and 24 follow anti-CD3/anti-CD28 magnetic bead stimulation and chimeric antigen receptor transduction.
Project description:Second-generation CD19-targeted chimeric antigen receptors (CAR) have an antigen-binding domain fused to transmembrane, co-stimulatory, and CD3ζ domains. The two CARs with regulatory approval include a CD28 or 4-1BB co-stimulatory domain. While both CARs achieve similar clinical outcomes, biologic differences between the two endodomains have become apparent but not completely understood. The objective is to evaluate gene expression in different mouse CD19-targeted CAR T cells, including m19z, m1928z and m19-humBBz.
Project description:Second-generation CD19-targeted chimeric antigen receptors (CAR) have an antigen-binding domain fused to transmembrane, co-stimulatory, and CD3ζ domains. The two CARs with regulatory approval include a CD28 or 4-1BB co-stimulatory domain. While both CARs achieve similar clinical outcomes, biologic differences between the two endodomains have become apparent but not completely understood. The objective is to evaluate gene expression in different mouse CD19-targeted CAR T cells, including m19z, m1928z and m19-musBBz.