Calibrated CAR activation potential directs alternative T cell fates and therapeutic potency
UID: 10576
- Description
- Summary from the GEO: "CD19-specific CARs that comprise CD28 and CD3z signaling domains program highly performing effector functions that mediate potent tumor elimination, but they impart a relatively limited T cell lifespan. Increasing functional T cell persistence without reducing effector potency is therefore likely to further enhance the therapeutic success of 1928z CAR T cells. We demonstrate that the number and position of ITAMs in 1928z CAR T cells influence functional, phenotypic and transcriptional programs, resulting in profound effects on antitumor efficacy. Improved therapeutic potency of CAR T cells can thus be achieved by calibrating activation strength, thereby retaining memory functions and preventing exhaustion, without compromising effector functions. Our transcriptional analysis underscores the potential of ITAM dosage and position to direct different T cell fates. We were able to identify a novel CAR design, termed 1XX, which programs a favorable balance of effector and memory signatures, inducing increased persistence of highly functional CARs with the replicative capacity of long-lived memory cells and potent effector functions.
In order to assess the different phenotypic and functional patterns of CARs encoding a single immunoreceptor tyrosine-based activation motif (ITAM), we compared the genome-wide transcriptional profiles of 1928z, 1XX and XX3 after CD19 antigen stimulation of TRAC-edited naïve T cells. Sorted naïve (TN), stem cell memory (TSCM) and effector (TEFF) CD8+ T cells served as controls."
-
Access via GEO
Plain Text sequencing data.
Accession #: GSE121226Access via SRARNA Sequence reads for 27 samples.
Accession #: SRP165725Access via BioProjectAdditional information about overall initiative.
Accession #: PRJNA496405 - Access Restrictions
-
Free to All
- Access Instructions
- The NCBI Gene Expression Omnibus, SRA, and BioProject databases provide open access to these files.
- Associated Publications
- Data Type
- Equipment Used
- Dataset Format(s)
- Plain Text, SRA, gzip
- Dataset Size
- 3.8 Mb (GZIP of TXT), 231.65 Gb (SRA)
Do you have or know of a dataset that should be added to the catalog? Let us know!