GEO DataSets

(Submitter supplied) An obstacle with continued clinical development of CAR T cells is the limited understanding of CAR T cell biology and its mechanisms of anti-tumor immunity. We and others have shown that CARs with a CD28 co-stimulatory domain drive high levels of T cell activation that also lead to exhaustion and shortened persistence. This led us to hypothesize that by incorporating null mutations of CD28 subdomains (YMNM, PRRP, or PYAP) we could optimize CAR T cell signaling and reduce exhaustion. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL19057

12 Samples

Download data: BED, TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

28 Samples

Download data

(Submitter supplied) Second generation (2G) chimeric antigen receptors (CARs) contain a CD28 or 41BB co-stimulatory endodomain and elicit remarkable efficacy in hematological malignancies. Third generation (3G) CARs extend this linear blueprint by fusing both co-stimulatory units in series. However, clinical impact has been muted despite compelling evidence that co-signaling by CD28 and 41BB can powerfully amplify natural immune responses. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL29417

48 Samples

Download data: RCC

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

14 Samples

Download data

(Submitter supplied) Chimeric antigen receptor (CAR)-T cell therapy targeting human CD19 have demonstrated clinical efficacy against B-cell malignancies. However, CAR-T cell therapy's efficacy against solid tumors is limited due to factors like low tumor-associated antigens, infiltration rate, and T cell exhaustion. We have shown that deleting NR4a genes in CAR-T cells prevents T cell exhaustion and improved their therapeutic effects on solid tumors in a mouse model. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

14 Samples

Download data: TSV, TXT

(Submitter supplied) 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. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL16686

36 Samples

Download data: CEL, CHP

(Submitter supplied) Vγ9Vδ2 T cells are an attractive cell platform for the off-the-shelf cancer immunotherapy due to their lack of alloreactivity and inherent multi-pronged cytotoxicity, which could be further amplified with chimeric antigen receptors (CARs). In this study, we sought to enhance the in vivo longevity of CAR-Vδ2 T cells by modulating ex vivo manufacturing conditions and selecting an optimal CAR costimulatory domain. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

8 Samples

Download data: TXT

(Submitter supplied) The objective of this experiment was to characterized the molecular mechanisms behind the different effects of PD-1 disruption in low affinity (LA) and high affinity (HA) HER2-28z CAR-T cells. The transcriptomic profile of mock and PD-1 KO CAR-T cells following antigen recognition was compared by using the nCounter® CAR-T Characterization Gene Expression Panel (Nanostring). RNA samples were isolated from CAR-T cells generated from three independent donors.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL32141

12 Samples

Download data: RCC

(Submitter supplied) The adoptive transfer of chimeric antigen receptor- (CAR) modified T cells is revolutionizing the treatment of B cell malignancies and has the potential to be applied to other diseases. CARs redirect T cell specificity by linking an antigen recognition domain to T cell signaling modules comprised of CD3z to provide signal 1, and CD28 or 4-1BB to provide costimulation. CD28/CD3z and 4-1BB/CD3z CARs confer differences in effector function and cell fate that affect clinical efficacy and toxicity. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

24 Samples

Download data: CSV

(Submitter supplied) Human T cells isolated from healthy donors were transduced with non-tonically signaling CARs or tonically signaling CARs, each with CD28z or 4-1BB costimulatory domains

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

15 Samples

Download data: CEL, CHP

(Submitter supplied) Chimeric antigen receptor–T (CAR-T) cell therapies can eliminate relapsed and refractory tumors, but the durability of antitumor activity requires in vivo persistence. Differential signaling through the CAR costimulatory domain can alter the T cell metabolism, memory differentiation, and influence long-term persistence. CAR-T cells costimulated with 4-1BB or ICOS persist in xenograft models but those constructed with CD28 exhibit rapid clearance. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL23227

6 Samples

Download data: TXT

(Submitter supplied) Single cell gene expression profile of WT and SUV39H1-edited CAR T cells at pre-infusion (Day 0), day 9 and day 16 post infusion in tumor (NALM6) bearing NSG mice

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Other

Platform:

GPL24676

48 Samples

Download data: RDS

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL20301 GPL24676

64 Samples

Download data

(Submitter supplied) Comparing genome accessibility profiles (ATACseq) of WT and SUV39H1-edited CAR T cells

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL20301

6 Samples

Download data: TXT

(Submitter supplied) Comparing transcriptional profiles (RNAseq) of WT and SUV39H1-edited CAR T cells

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL20301

10 Samples

Download data: TXT

(Submitter supplied) CD19-targeted Chimeric antigen receptor T cells (CART) cells have shown remarkable promise in various B cell malignancies. Sustained tonic signaling and antigen exposure drives CART cell differentiation and exhaustion, which limits the therapeutic potency and persistence of CART cells and is a major cause of CD19-expressing leukemia relapse after CD19-targeted CART cells treatment in ALL. Here, we systematically screened FDA approved tyrosine kinase inhibitors, and identified dasatinib as the best candidate to prevent or reverse both CD28/CART and 4-1BB/CART cells from differentiation and exhaustion during ex vivo expansion, which enhanced the therapeutic efficacy and in vivo persistence. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

8 Samples

Download data: CSV

(Submitter supplied) CAR T-cell therapy for solid tumors has shown limited efficacy in early phase clinical studies. The majority of CARs encode CD28 and/or 41BB costimulatory endodomains and we explored here if MyD88 and CD40 (MC) costimulatory endodomains in CARs improve their antitumor activity. We generated CD28-, 41BB-, and MC-CAR T-cells and demonstrate that MC-CAR T-cells have greater proliferative capacity and antitumor activity in repeat stimulation assays and in tumor models in vivo. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

48 Samples

Download data: TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing

Platforms:

GPL20301 GPL24676 GPL18573

89 Samples

Download data

(Submitter supplied) Chimeric antigen receptor (CAR) engineered T cells often fail to enact effector functions after infusion into patients. Understanding the biological pathways that lead CAR T cells to failure is of critical importance in the design of more effective therapies. We developed and validated an in vitro model that drives T cell dysfunction by chronic CAR stimulation and interrogated how CAR costimulatory domains contribute to T cell failure. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL20301

6 Samples

Download data: MTX, TSV

(Submitter supplied) Chimeric antigen receptor (CAR) engineered T cells often fail to enact effector functions after infusion into patients. Understanding the biological pathways that lead CAR T cells to failure is of critical importance in the design of more effective therapies. We developed and validated an in vitro model that drives T cell dysfunction by chronic CAR stimulation and interrogated how CAR costimulatory domains contribute to T cell failure. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

65 Samples

Download data: TXT