Expression data from mouse CD19-targeted CAR (chimeric antigen receptor) T cells after antigen stimulation [expression array]
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ABSTRACT:
PROVIDER: PRJNA437645 | ENA |
REPOSITORIES: ENA
Similar Datasets
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.
2018-07-31 | GSE111641 | GEO
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.
2018-07-31 | GSE112566 | GEO
Project description:Expression data from mouse CD19-targeted CAR (chimeric antigen receptor) T cells after antigen stimulation
| PRJNA448188 | ENA
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. 30 samples were submitted. Samples represented three biological replicates of normal donors transduced with various CARs. CARs used were a cMet 28z specific CAR comprised of the IgG4 hinge, CD28 transmembrane and CD28 and CD3zeta intracellular domains. A CD19 CD28 CAR was specific to CD19, and was comprised of a CD8a hinge, CD28 transmembrane and CD28 and CD3zeta intracellular domain. A third CAR, the CD19 BBz, was used that was specific to CD19 was comprised of a CD8a hinge, CD8a transmembrane and 4-1BB and CD3zeta intracellular domains. Expression data was analyzied on day 0, 6, 11 and 24.
2015-01-14 | E-GEOD-64914 | biostudies-arrayexpress
Project description:Expression data from mouse CD19-targeted CAR (chimeric antigen receptor) T cells after antigen stimulation [RNA-seq]
| PRJNA448192 | ENA
Project description:Adoptive transfer of anti-CD19 chimeric antigen receptor (CAR)-engineered T cells has shown impressive clinical responses in patients with refractory B-cell malignancies. However, therapeutic effects of CAR-T cells targeting other hematologic malignancies and solid tumors are not yet satisfactory. Although inefficient tumor trafficking and multiple immunosuppressive molecules impede CAR-T cell effector responses, signals delivered by the current CAR constructs may still be insufficient to fully activate antitumor T cell functions. Optimal T cell activation and proliferation requires multiple signals including T cell receptor (TCR) engagement (signal 1), costimulation (signal 2), and cytokine engagement (signal 3). CAR genes developed to date contain a CD3z domain and costimulatory domain(s), but not a domain to transmit signal 3. In this study, we have developed a novel CAR construct capable of inducing cytokine signaling in an antigen-dependent manner. The new generation CD19 CAR encodes a cytoplasmic domain of IL-2RB and STAT3-binding YXXQ motif together with CD3z and CD28 domains (28-IL2RB-z (YXXQ)). The 28-IL2RB-z (YXXQ) CAR-T cells showed antigen-dependent JAK-STAT, especially the STAT3-mediated pathway activation, which promoted their proliferation and prevented terminal differentiation. The 28-IL2RB-z (YXXQ) CAR-T cells demonstrated superior in vivo persistence and antileukemia effects compared with the currently used CARs in multiple tumor models.
2020-02-15 | GSE95037 | GEO
Project description:Adoptive transfer of anti-CD19 chimeric antigen receptor (CAR)-engineered T cells has shown impressive clinical responses in patients with refractory B-cell malignancies. However, therapeutic effects of CAR-T cells targeting other hematologic malignancies and solid tumors are not yet satisfactory. Although inefficient tumor trafficking and multiple immunosuppressive molecules impede CAR-T cell effector responses, signals delivered by the current CAR constructs may still be insufficient to fully activate antitumor T cell functions. Optimal T cell activation and proliferation requires multiple signals including T cell receptor (TCR) engagement (signal 1), costimulation (signal 2), and cytokine engagement (signal 3). CAR genes developed to date contain a CD3z domain and costimulatory domain(s), but not a domain to transmit signal 3. In this study, we have developed a novel CAR construct capable of inducing cytokine signaling in an antigen-dependent manner. The new generation CD19 CAR encodes a cytoplasmic domain of IL-2RB and STAT3-binding YXXQ motif together with CD3z and CD28 domains (28-DIL2RB-z (YXXQ)). The 28-DIL2RB-z (YXXQ) CAR-T cells showed antigen-dependent JAK-STAT, especially the STAT3-mediated pathway activation, which promoted their proliferation and prevented terminal differentiation. The 28-DIL2RB-z (YXXQ) CAR-T cells demonstrated superior in vivo persistence and antileukemia effects compared with the currently used CARs in multiple tumor models.
2018-01-21 | GSE103906 | GEO
Project description:To characterize transfer of molecules from target cells into CAR T cells via trogocytosis we cultured NALM-6 leukemia cell line expressing a CD19-mCherry fusion protein with CAR T cells. NALM6-CD19-mCherry were loaded with heavy amino acid and cocultured with CAR T cells for 1 hour. CAR T cells were next sorted into two fractions, mCherry-positive (TrogPos), and -negative (TrogNeg). Proteomics analysis revealed the presence of targeted antigen (CD19) in the TrogPos only.
2019-03-29 | PXD012833 | Pride
Project description:Chimeric antigen receptor (CAR)-expressing T-cells induce durable remissions in patients with relapsed/refractory B-cell malignancies. CARs are artificial constructs introduced into mature T-cells conferring a second, non-MHC restricted specificity in addition to the endogenous T-cell receptor (TCR). The impact of TCR activation on CAR T-cell efficacy in vivo has important implications for clinical optimization of CAR T-cell therapy, but cannot be systematically evaluated in xenograft models. Using an immunocompetent, syngeneic murine model of CD19-targeted CAR T-cell therapy for pre-B cell ALL, we demonstrate loss of CD8 CAR T-cell mediated clearance of leukemia associated with T-cell exhaustion and apoptosis when TCR antigen is present. CD4 CAR T-cells demonstrate equivalent cytotoxicity, as compared to CD8 CAR T-cells, and in contrast, retain in vivo efficacy in the presence of TCR stimulation. Gene expression profiles confirm increased exhaustion and apoptosis of CAR8 upon dual receptor stimulation compared to CAR4, and indicate inherent differences in T-cell pathways. Chimeric antigen receptor (CAR) T cells express two activating receptors, the CAR and the endogenous T cell receptor (TCR). CAR T cells can be derived from either CD8 or CD4 T cells to generate CAR8 and CAR4 cells, respectively. In vivo, CAR8 and CAR4 cells respond differently when simultaneously stimulated through the CAR and TCR.
2017-12-31 | GSE103632 | GEO
Project description:Chimeric antigen receptor (CAR) T-cells directed against CD19 (CART19) are effective in relapsed/refractory (R/R) B-cell malignancies. Not all patients show treatment efficacy, but little is known about the molecular factors predicting clinical outcome of CART19 therapy. Our objective was to determine the effect of epigenetic changes in CART19 cells on the clinical course of B-cell malignancy patients treated with adoptive therapy. We report a case series of B-cell malignancy patients (68 males (M) and 46 females (F); median age of 24 years (range 3-70 years)), comprising 77 acute lymphoblastic leukemia (ALL) cases and 37 non-Hodgkin lymphoma (NHL) cases, who were treated with CART19 cells. Using a DNA methylation microarray, we determined the epigenomic changes that occur in the patient T-cells upon transduction of the CAR vector. We identified 984 genomic sites with differential DNA methylation between CAR-untransduced (UT) and CAR-transduced (TD) T-cells before infusion into the patient. 18 of these distinct epigenetic loci were significantly associated with complete response (CR). Using the sites linked to CR, the EPICART signature was established, which was associated with enhanced overall survival (OS).
2021-08-23 | GSE179414 | GEO