Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single residue in CD28-costimulated CAR-T cells limits long-term persistence and antitumor durability

ABSTRACT: Single residue in CD28-costimulated CAR-T cells limits long-term persistence and antitumor durability

PROVIDER: PRJNA605702 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR11050726.fastq.gz	Fastqsanger.gz
	SRR11050727.fastq.gz	Fastqsanger.gz
	SRR11050728.fastq.gz	Fastqsanger.gz
	SRR11050729.fastq.gz	Fastqsanger.gz
	SRR11050730.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 6

Similar Datasets

Single residue in CD28-costimulated CAR-T cells limits long-term persistence and antitumor durability

Project description: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. Here, we show that a single amino acid residue in CD28 drove T cell exhaustion and hindered the persistence of CD28-based CAR-T cells and changing this asparagine to phenylalanine (CD28-YMFM) promoted durable antitumor control. In addition, CD28-YMFM CAR-T cells exhibited reduced T cell differentiation and exhaustion as well as increased skewing toward Th17 cells. Reciprocal modification of ICOS-containing CAR-T cells abolished in vivo persistence and antitumor activity. This finding suggests modifications to the costimulatory domains of CAR-T cells can enable longer persistence and thereby improve antitumor response.

2020-02-11 | GSE145007 | GEO

Single residue in CD28-costimulated CAR-T cells limits long-term persistence and antitumor durability.

Project description: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. Here, we show that a single amino acid residue in CD28 drove T cell exhaustion and hindered the persistence of CD28-based CAR-T cells and changing this asparagine to phenylalanine (CD28-YMFM) promoted durable antitumor control. In addition, CD28-YMFM CAR-T cells exhibited reduced T cell differentiation and exhaustion as well as increased skewing toward Th17 cells. Reciprocal modification of ICOS-containing CAR-T cells abolished in vivo persistence and antitumor activity. This finding suggests modifications to the costimulatory domains of CAR-T cells can enable longer persistence and thereby improve antitumor response.

| S-EPMC7260017 | biostudies-literature

Profiling of Naïve (CD45RA+CD28+), EM (CD45RA-CD28-) and TEMRA (CD45RA+CD28-) CD8+ T cells

Project description:Profiling of Naïve (CD45RA+CD28+), EM (CD45RA-CD28-) and TEMRA (CD45RA+CD28-) CD8+ T cells

| PRJNA530997 | ENA

Myeloid Niches Sustain Antitumor T Cells and License PD-1 Blockade via CD28 Costimulation

Project description:The local mechanisms regulating exhaustion of tumor-infiltrating lymphocytes (TILs) and responsiveness to PD-1 blockade remain partly elucidated. In human ovarian cancer we show that tumor-reactive intraepithelial (ie)CD8+ TILs engaged by antigen are polyfunctional and upregulate PD-1, which restrains their effectiveness. PD-1+ TILs exhibit a continuum of TCR-engaged/exhausted states with variable effector fitness related to CD28 costimulation, which they receive in intraepithelial niches involving myeloid antigen-presenting cells (mAPC). Following PD-1 blockade, activation of TILs requires CD28 costimulation mediated in situ by tumor mAPCs, which is locally enhanced by CTLA-4 blockade. CD40 ligand also amplifies TIL responses in situ, especially in tumors in which mAPCs are not activated. Thus, dysfunctional and exhausted TILs, in a state of TCR engagement but without proper CD28 costimulation by mAPCs in situ, are unlikely to fully benefit from PD-1 blockade.

2021-10-12 | GSE178245 | GEO

Inhibiting intracellular CD28 in cancer cells enhances antitumor immunity and overcomes anti-PD-1 resistance via targeting PD-L1

Project description:In vivo genome-wide CRISPR screening unraveled the non-classical role of cancer cell Cd28 in tumor immune escape, and identified cancer cell Cd28 as a novel target in breast cancer immunotherapy by modulating tumor immunogenicity and anti-tumor CD8+ T cell responses.

2024-12-26 | GSE232503 | GEO

Inhibiting intracellular CD28 in cancer cells enhances antitumor immunity and overcomes anti- PD-1 resistance via targeting PD-L1

2024-12-26 | GSE231792 | GEO

biogas residue compost

Project description:biogas residue compost Raw sequence reads

| PRJNA668224 | ENA

Inhibiting intracellular CD28 in cancer cells enhances antitumor immunity and overcomes anti-PD-1 resistance via targeting PD-L1

Project description:To determine how deficiency of Cd28 influences 4T1 cells, we performed a transcriptional analysis

2024-12-26 | GSE268610 | GEO

Interactomics of the RLTPR protein explain its essential role for costimulation via CD28

Project description:The RLTPR cytosolic protein has an essential role in CD28 costimulation but its mode of action and importance in human T cells remain elusive. Here, using mass spectrometry we showed that CD28, RLTPR and the CARMA1 cytosolic adaptor physically associate in mouse T cells. Although RLTPR is thought to function as an actin-uncapping protein, this property was dispensable for CD28 costimulation. Our findings underpin the convergent function of RLTPR in T cells and suggest that its scaffolding role predominates during CD28 costimulation.

2016-09-27 | PXD003870 | Pride

Profiling of Naïve (CD45RA+CD28+), EM (CD45RA-CD28-) and TEMRA (CD45RA+CD28-) CD8+ T cells from kidney transplanted patients

Project description:Profiling of Naïve (CD45RA+CD28+), EM (CD45RA-CD28-) and TEMRA (CD45RA+CD28-) CD8+ T cells from kidney transplanted patients

| PRJNA814511 | ENA