Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Hierarchical ZIF-8@Au cluster Nanocarriers for In Situ CAR-M programming and Immunotherapy in Prostate Cancer

ABSTRACT: Here, we have successfully constructed a novel nano-delivery system based on the Zeolitic Imidazolate Framework-8 (ZIF-8), which revealed high CAR gene encapsulation efficiency, reduced non-specific hepatic accumulation, targeted delivery of tumor-associated macrophages (TAM) and efficient intracellular gene transfection efficiency enable the in-situ construction of CAR-M cells. Meanwhile, the co-delivery of the IFN-γ and CAR genes not only maintains the specific killing and phagocytic activity of CAR-M against tumor cells but also activates the adaptive immunity, inducing excellent anti-tumor efficacy in a prostate cancer mouse model. In summary, this strategy provides a novel approach for the systematic in vivo editing of CAR-M.

ORGANISM(S): Mus musculus

PROVIDER: GSE298594 | GEO | 2025/05/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Hierarchical ZIF-8@Au cluster Nanocarriers for In Situ CAR-M programming and Immunotherapy in Prostate Cancer

Project description:Hierarchical ZIF-8@Au cluster Nanocarriers for In Situ CAR-M programming and Immunotherapy in Prostate Cancer

| PRJNA1269994 | ENA

Gene expression profiling of sarcoma cells treated with mithramycin A (MTA), nano-encapsulated MTA or MTA-analogs

Project description:This study was designed to gain insight about the mechanisms involved in the anti-tumor effects of mithramycin A (MTA) and the MTA analog EC-8042 in sarcoma cells. In addition, we also studied whether this molecular features could be influenced by the nano-encapsulation of MTA.

2021-03-30 | GSE161616 | GEO

Zeolitic Imidazolate Frameworks Activate Endosomal Toll-like Receptors and Potentiate Immunogenicity of SARS-CoV-2 Spike Protein Trimer

Project description:Nanomaterials offer new opportunities to engineer immunomodulatory activity. In this work, we report the endosomal toll-like receptor agonist activity of a nanoscale adjuvant zeolitic imidazolate frameworks-8 (ZIF-8). The accumulation of ZIF-8 in endosomes and the pH-responsive release of its subunits enable selective engagement with endosomal TLRs, minimizing the risk of off-target activation. The intrinsic adjuvant properties of ZIF-8, along with the efficient delivery and biomimetic presentation of a SARS-CoV-2 spike protein receptor binding domain trimer, primed rapid humoral and cell mediated immunity in a dose sparing manner. Our study offers new insights for next-generation adjuvants that can potentially impact future vaccine development.

2024-03-13 | GSE246178 | GEO

Single cell RNA sequencing of CD45.2+ endogenous immune cells following treatment with CAR-T cells

Project description:The goal of this study was to assess the consequences of RNA delivery via CAR-T cell on endogenous immune cells within the B16 tumor microenvironment. RN7SL1 RNA-producing CAR-T cells are the relevant experimental condition, while control scramble RNA and No RNA 19BBz CAR-T cells are also included.

2021-09-01 | GSE179253 | GEO

Ex Vivo Expansion and Hydrogel-Mediated In Vivo Delivery of Tissue Resident Memory T Cells for Immunotherapy

Project description:Tissue-resident memory (TRM) T cells preferentially reside in peripheral tissues, serving as key players in tumor immunity and immunotherapy. Currently, the lack of effective approaches for expanding TRM cells and delivering these cells in vivo hinder the exploration of TRM cell-mediated cancer immunotherapy. Here, we report a nanoparticle artificial antigen-presenting cell (nano-aAPC) ex vivo expansion approach and an in vivo delivery system for TRM cells. Using the nano-aAPC platform, we expanded functional antigen-specific murine and human TRM-like CD8+ T cells ex vivo. We also developed an injectable macroporous hyaluronic acid (HA) hydrogel for delivery of TRM-like cells. TRM-like cells delivered in the optimized HA hydrogel trigger robust local and systemic antitumor immunity and show synergistic effect with anti-PD1 treatment. Our findings suggest that nano-aAPC-induced TRM-like cells, coupled with a hydrogel delivery system, offer an efficient way to advance the understanding of TRM cells-mediated cancer therapy.

2024-06-04 | GSE267822 | GEO

Optimizing Non-Viral Gene Delivery to T Cells with Lipofectamine LTX

Project description:Retroviral gene delivery is widely used in CAR-T cell therapies for hematological cancers. However, viral vectors are expensive to manufacture, integrate genes in semi-random patterns, and their transduction efficiency is highly variable. In contrast, non-viral delivery methods could offer a potentially less expensive and safer alternative for CAR-T cell gene delivery. In this study, several different cationic vehicles, promoters, and additional culture conditions were compared to optimize non-viral transgene delivery and expression in both Jurkat and primary T cells. In addition, confocal microscopy and next-generation sequencing experiments were also conducted to detect putative methods of transfection resistance in Jurkat and primary T cells. Transfecting Jurkat cells in X-VIVOTM 15 media with Lipofectamine LTX provided a high transfection efficiency in Jurkat cells (63.0±10.9% EGFP+). However, this protocol yielded a much lower transfection efficiency (8.07±0.76% EGFP+) in primary T cells. Confocal microscopy and mRNA-sequencing experiments revealed that a majority of lipoplexes did not enter the primary T cells, perhaps due to relatively low expression levels of heparan sulfate proteoglycans (HSPGs). Primary T cells also expressed high levels of PYHIN DNA sensors (e.g., AIM2, IFI16), which can induce apoptosis when bound to cytoplasmic DNA. Primary T cells are more resistant to transfection with Lipofectamine than Jurkat T cells. Transfection of primary T cells appears to be hindered by decreased expression of HSPGs and high expression of PYHIN DNA sensors. Both of these factors should be considered in the development of future viral and non-viral T cell gene delivery methods.

2020-06-04 | GSE151759 | GEO

Efficient arming of memory-like NK cells with a TCR-like CAR for treating acute myeloid leukemia with NPM1 mutation

Project description:We showed Cytokine induced memory-like (CIML) human NK cells have higher trasduction efficiency with CAR lentivirus for therapeutics. We performed single cell RNAseq analysis to comprehensively understand the transcripttion difference between NPM1c-CAR-mb15 CIML NK cells and CAR-negative CIML NK cells, as well as their transcriptional response to NPM1c+ AML tumor cells.

2021-10-26 | GSE186115 | GEO

Chimeric Antigen Receptor-Macrophage Extracellular Vesicles Reprogram Immune Microenvironment for Cancer Therapy

Project description:Immunotherapy has become a new milestone in cancer treatment, with chimeric antigen receptor (CAR)-T cell therapy proven to be an effective method for treating hematologic malignancies. However, its efficacy in solid tumors remains limited. Macrophages, the most infiltrative innate immune cells in the tumor microenvironment, are being genetically engineered to express CARs, rapidly emerging as a promising new therapy for non-hematologic malignancies. Yet, CAR- Macrophages therapy is associated with unique acute toxicities and is susceptible to immunosuppressive mechanisms. Here, we propose using CAR macrophages-derived extracellular vesicles (CAR-MEVs) as an optimization of CAR-Ms therapy. Compared to CAR-Ms cells, CAR-MEVs exhibit lower toxicity and enhanced drug delivery capabilities. In an in vivo liver cancer model, CAR-MEVs administration proved safer than CAR-Ms therapy, reducing tumor burden and prolonging overall survival. In a humanized mouse model, CAR-MEVs further demonstrated the ability to induce a pro-inflammatory tumor microenvironment and enhance anti-tumor T cell activity. Mechanistically, CAR-MEVs target tumor cells, inducing immunogenic cell death (ICD) and subsequently leading to neutrophil infiltration in tumor tissues. We demonstrated that the anti-tumor effects of CAR-MEVs depend on neutrophils and are partially reliant on inducible nitric oxide synthase (iNOS). This study supports the potential of macrophage extracellular vesicles as a novel therapeutic approach for solid tumors.

2025-02-21 | GSE275346 | GEO

CAR gene delivery by T-cell targeted lentiviral vectors is enhanced by rapamycin induced reduction of antiviral mechanisms

Project description:Lentiviral vectors (LV) have become the dominant tool for stable gene transfer into lymphocytes including chimeric antigen receptor (CAR) gene delivery to T cells, a major breakthrough in cancer therapy. Yet, room for improvement remains, especially for the latest LV generations delivering genes selectively into T cell subtypes, a key requirement for in vivo CAR T cell generation. Towards improving gene transfer rates with these vectors, we conducted whole transcriptome analyses on human T lymphocytes after exposure to CAR-encoding conventional vector VSV-LV, and vectors targeted to CD8+ (CD8-LV) or CD4+ T cells (CD4-LV). Genes related to quiescence and antiviral restriction were found to be upregulated in CAR-negative cells exposed to all types of LVs. Down-modulation of various antiviral restriction factors including the interferon-induced transmembrane proteins (IFITMs) was achieved with rapamycin as verified by mass spectrometry (LC-MS). Strikingly, rapamycin enhanced transduction by up to 7-fold for CD8-LV and CD4-LV without compromising CAR T cell activities, but did not improve VSV-LV. When administered to humanized mice, CD8-LV resulted in higher rates of GFP gene delivery as well as faster in vivo CAR T cell generation and tumor control. The data favors multi-omics approaches for improvements in gene delivery.

2023-12-20 | GSE228824 | GEO

Human astrocyte encapsulation for delivery of cytokines to modulate neuroinflammation

Project description:Human astrocyte encapsulation for delivery of cytokines to modulate neuroinflammation

| PRJNA1149756 | ENA