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RESET: A reversible TCR-coupled antigen receptor with superior targeting sensitivity and pharmacologically controlled anti-tumor activity

ABSTRACT: RESET: A reversible TCR-coupled antigen receptor with superior targeting sensitivity and pharmacologically controlled anti-tumor activity

PROVIDER: PRJNA1200012 | ENA |

REPOSITORIES: ENA

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RESET: A reversible TCR-coupled antigen receptor with superior targeting sensitivity and pharmacologically controlled anti-tumor activity

Project description:Chimeric antigen receptor (CAR) T cells are effective cancer therapies, particularly in indications with high, stable, and tumor-specific antigen expression. Other settings may require improved targeting sensitivity, controllable targeting selectivity, and/or additional potency enhancements to achieve robust efficacy. Here, we describe a novel receptor architecture called RESET (rapamycin-enabled, switchable endogenous T-cell receptor) that combines: (i) cell surface antigen targeting; (ii) small-molecule regulation; and (iii) the signaling proficiency and inherent sensitivity of native T-cell receptors. RESET-T cells outperformed both constitutive and drug-regulated CAR-T cells and show hallmarks of TCR activation that suggest improved fidelity to native T-cell responses. Pharmacological control then increases safety through toggling T-cell activation between active and resting states and may mitigate T- cell exhaustion caused by continuous antigen exposure. This convergence of drug-regulated targeting and natural immune receptor signal transduction may better replicate the kinetics and physiology of a classical T-cell responses and potentiate more successful and safer immunotherapies.

2025-04-23 | GSE284664 | GEO

RNA-seq of chemically reset human naive pluripotent stem cells

Project description:A simple method is presented to reset human pluripotent cells to a naive state via transient histone deacetylase inhibition and maintenance in chemically-defined naive stem cell culture media. Cells can be reset without transgenes and expanded continuously either on feeders or alternative substrates in feeder-free conditions. Multiple cell lines of varying origin were reset and characterised in parallel with conventionally cultured counterparts.

2017-08-07 | E-MTAB-5674 | biostudies-arrayexpress

Reproduction of reset cell

Project description:Functional-assay limitations are an emerging issue in characterizing human pluripotent stem cells (hPSCs). With rodent PSCs, chimera formation, using pre-implantation embryos, is the gold-standard assay of pluripotency. In hPSCs, this can only be monitored via teratoma formation or in vitro differentiation, as ethical concerns preclude generation of human-animal chimera. To circumvent this issue, we established a functional assay utilizing interspecific blastocyst injection and in vitro culture (interspecies in vitro chimera assay). The assay uses mouse pre-implantation embryos and human PSCs to make interspecies chimeras cultured in vitro to the early egg cylinder stage. When hiPSCs, both conventional and naive type, which called M-bM-^@M-^\reset cellM-bM-^@M-^], were injected into mouse embryos and cultured. The cells were never integrated into the epiblast of egg cylinder stage-embryo. These results suggest that hPSCs, including naM-CM-/ve type, are unable to form chimera with mouse embryo. Reset cells were converted from conventional human iPSC line PB004, and then compared their gene expression profile with or without transgene overexpression induced by doxycyclin treatment.

2015-03-10 | E-GEOD-66657 | biostudies-arrayexpress

Microarray expression profiling of conventional and reset human pluripotent stem cells

Project description:Human pluripotent cells were reset to ground state pluripotency by transient overexpression of NANOG and KLF2 and subsequent inhibition of ERK and protein kinase C. Transcriptional profiling of H9 parental and clonal lines, and induced pluripotent stem cells derived from adult fibroblast and adipose cell types was carried out in reset and conventional culture conditions.

2014-09-10 | E-MTAB-2856 | biostudies-arrayexpress

RNA sequencing of conventional and reset human pluripotent stem cells

Project description:Human pluripotent cells were reset to ground state pluripotency by transient overexpression of NANOG and KLF2 and subsequent inhibition of ERK and protein kinase C. Transcriptional profiling of reset cells and conventional pluripotent stem cell cultures was carried out by RNA-seq, in tandem with mouse embryonic stem cells propagated under similar conditions to assess the combinatorial effects of MEK inhibitor PD0325901, GSK3 inhibitor CHIR99021 and PKC inhibitor Go6983.

2014-09-10 | E-MTAB-2857 | biostudies-arrayexpress

Reproduction of reset cell

Project description:Functional-assay limitations are an emerging issue in characterizing human pluripotent stem cells (hPSCs). With rodent PSCs, chimera formation, using pre-implantation embryos, is the gold-standard assay of pluripotency. In hPSCs, this can only be monitored via teratoma formation or in vitro differentiation, as ethical concerns preclude generation of human-animal chimera. To circumvent this issue, we established a functional assay utilizing interspecific blastocyst injection and in vitro culture (interspecies in vitro chimera assay). The assay uses mouse pre-implantation embryos and human PSCs to make interspecies chimeras cultured in vitro to the early egg cylinder stage. When hiPSCs, both conventional and naive type, which called “reset cell”, were injected into mouse embryos and cultured. The cells were never integrated into the epiblast of egg cylinder stage-embryo. These results suggest that hPSCs, including naïve type, are unable to form chimera with mouse embryo.

2015-03-10 | GSE66657 | GEO

McKay reversible p53 response

Project description:Reversible p53 activation using a temperature variant of p53

2012-04-30 | E-MEXP-3224 | biostudies-arrayexpress

RNA sequencing of conventional and reset human pluripotent stem cells

Project description:RNA sequencing of conventional and reset human pluripotent stem cells

| PRJEB7132 | ENA

RNA-seq of chemically reset human naive pluripotent stem cells

Project description:RNA-seq of chemically reset human naive pluripotent stem cells

| PRJEB20388 | ENA

Gene expression analysis of prostate tumors arisen in TRAMP mice in which mast cells are pharmacologically stabilized or genetically ablated.

Project description:Analysis of gene expression of prostate tumors arisen in TRAMP mice in which mast cells are pharmacologically stabilized or genetically ablated.The hypothesis tested in the present study was that mast cells inhibition or absence impacted prostate tumor development and histotype. Results demonstrate that prostate tumors arisen in TRAMP mice in which mast cells are pharmacologically stabilized or genetically ablated have a neuroendocrine signature. Total RNA obtained from prostate tumors from 24 wks old TRAMP mice chronically treated with sodium chromoglycate (cromolyn) since 8 wks of age, and from 24 wks old TRAMP KitW-sh mice, compared to untreated 30 wks old TRAMP mice and to non tumoral prostates

2011-06-15 | E-GEOD-29956 | biostudies-arrayexpress

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