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Epigenetically programmed ‘stem-like’ tissue resident memory CAR T-cells exhibit robust activity against solid and liquid tumors

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE224866 | GEO | 2023/02/23

REPOSITORIES: GEO

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Epigenetically programmed ‘stem-like’ tissue resident memory CAR T-cells exhibit robust activity against solid and liquid tumors [bulk_RNA]

Project description:Chimeric antigen receptor (CAR) T-cells have shown remarkable success in the therapy of hematological malignancies, but they have not yet proven nearly as effective in treating non-hematopoietic cancers. This study proposes augmentation of CAR T-cell function and accumulation in solid tumors by modifying the epigenetic landscape that governs early memory differentiation and adaptation to tissue residency. We identified that a key factor in human tissue-resident memory CAR T-cell (CAR-TRM) formation is activation in the presence of the pleotropic cytokine, TGF-β, which epigenetically enforces a core transcriptional program of both ‘stemness’ and sustained tissue residency. This strategy results in a readily actionable in vitro production method for engineering peripheral blood T-cells into large numbers of ‘stem-like’ CAR-TRM cells resistant to epigenetically-imposed exhaustion that possess enhanced ability to accumulate in situ and rapidly kill cancer cells for more effective immunotherapy.

2023-02-23 | GSE224864 | GEO

Epigenetically programmed ‘stem-like’ tissue resident memory CAR T-cells exhibit robust activity against solid and liquid tumors [bulk_ATAC]

2023-02-23 | GSE224862 | GEO

Epigenetically programmed ‘stem-like’ tissue resident memory CAR T-cells exhibit robust activity against solid and liquid tumors [scRNA]

2023-02-23 | GSE224865 | GEO

Epigenetically programmed ‘stem-like’ tissue resident memory CAR T-cells exhibit robust activity against solid and liquid tumors

Project description:Epigenetically programmed ‘stem-like’ tissue resident memory CAR T-cells exhibit robust activity against solid and liquid tumors

| PRJNA932809 | ENA

Epigenetically programmed ‘stem-like’ tissue resident memory CAR T-cells exhibit robust activity against solid and liquid tumors [bulk_RNA]

Project description:Epigenetically programmed ‘stem-like’ tissue resident memory CAR T-cells exhibit robust activity against solid and liquid tumors [bulk_RNA]

| PRJNA934556 | ENA

Epigenetically programmed ‘stem-like’ tissue resident memory CAR T-cells exhibit robust activity against solid and liquid tumors [bulk_ATAC]

Project description:Epigenetically programmed ‘stem-like’ tissue resident memory CAR T-cells exhibit robust activity against solid and liquid tumors [bulk_ATAC]

| PRJNA934508 | ENA

Epigenetically programmed ‘stem-like’ tissue resident memory CAR T-cells exhibit robust activity against solid and liquid tumors [scRNA]

Project description:Epigenetically programmed ‘stem-like’ tissue resident memory CAR T-cells exhibit robust activity against solid and liquid tumors [scRNA]

| PRJNA934555 | ENA

Tissue-resident memory CAR T cells with stem-like characteristics display enhanced efficacy against solid and liquid tumors.

Project description:Chimeric antigen receptor (CAR) T cells demonstrate remarkable success in treating hematological malignancies, but their effectiveness in non-hematopoietic cancers remains limited. This study proposes enhancing CAR T cell function and localization in solid tumors by modifying the epigenome governing tissue-residency adaptation and early memory differentiation. We identify that a key factor in human tissue-resident memory CAR T cell (CAR-TRM) formation is activation in the presence of the pleotropic cytokine, transforming growth factor β (TGF-β), which enforces a core program of both "stemness" and sustained tissue residency by mediating chromatin remodeling and concurrent transcriptional changes. This approach leads to a practical and clinically actionable in vitro production method for engineering peripheral blood T cells into a large number of "stem-like" CAR-TRM cells resistant to tumor-associated dysfunction, possessing an enhanced ability to accumulate in situ and rapidly eliminate cancer cells for more effective immunotherapy.

| S-EPMC10313923 | biostudies-literature

B7-H3-Targeted CAR-Vδ1T Cells Exhibit Potent Broad-Spectrum Activity Against Solid Tumors

Project description:Vδ1T cells, a rare subset of γδT cells, hold promise for treating solid tumors. Unlike conventional T cells, they recognize tumor antigens independently of the MHC antigen-presentation pathway, making them a potential “off-the-shelf” cell therapy product. However, isolation and activation of Vδ1T cells is challenging, which has limited their clinical investigation. Here, we developed a large-scale clinical-grade manufacturing process for Vδ1T cells and validated the therapeutic potential of B7-H3-CAR-modified Vδ1T cells in treating solid tumors. Co-expression of interleukin-2 with the B7-H3-CAR led to durable anti-tumor activity of Vδ1T cells in vitro and in vivo. In multiple subcutaneous and orthotopic mouse xenograft tumor models, a single intravenous administration of the CAR-Vδ1T cells resulted in complete tumor regression. These modified cells demonstrated significant in vivo expansion and robust homing ability to tumors, akin to natural tissue-resident immune cells.Additionally, the B7-H3-CAR-Vδ1T cells exhibited a favorable safety profile. In conclusion, B7-H3-CAR-modified Vδ1T cells represent a promising strategy for treating solid tumors.

2024-08-22 | GSE275242 | GEO

CAR-T cells targeting CD38 and LMP1 exhibit robust antitumour activity against NK/T cell lymphoma.

Project description:BackgroundNatural killer/T cell lymphoma (NKTCL) is an aggressive lymphoma with a poor prognosis. Chimeric antigen receptor-transduced T (CAR-T) cell therapy has become a promising immunotherapeutic strategy against haematologic malignancies.MethodsIn this study, four CAR-T cell lines (CD38-CAR, LMP1-CAR, CD38-LMP1 tandem CAR 1 and CD38-LMP1 tandem CAR 2) were generated. The effect of CAR-T cells against NKTCL cells was evaluated both in vitro and in vivo. Expression of T cell activation markers and cytokines produced by CAR-T cells were detected by flow cytometry.ResultsThe four CAR-T cell lines could effectively eliminate malignant NKTCL cells. They could be activated and produce inflammatory cytokines in a target-dependent manner. In vivo tests showed that the CAR-T cells exhibited significant antitumour effects in a xenotransplanted NKTCL mouse model.ConclusionsIn summary, four CAR-T cell lines exhibited significant cytotoxicity against NKTCL cells both in vitro and in vivo. These results indicated the effective therapeutic promise of CD38 and LMP1 CAR-T cells in NKTCL.

| S-EPMC10470138 | biostudies-literature

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