Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Using an RNA-binding antibody for tumor-directed immunogenic RNA delivery

ABSTRACT: The inability to selectively deliver therapeutic RNAs within target cells currently hinders the development of novel treatments for cancer and other disorders. Here, we report that a tumor-targeting, cell-penetrating, and RNA-binding antibody, TMAB3, can form non-covalent antibody/RNA complexes that mediate highly specific and functional delivery of RNAs into tumors. We observed a robust anti-tumor efficacy of systemically administered 3p-hpRNA, an agonist of viral RNA sensor RIG-I, in complex with TMAB3 in animal models of pancreatic cancer, medulloblastoma, and melanoma. In pancreatic cancer models, treatment with TMAB3/3p-hpRNA tripled animal survival, decreased tumor growth, and specifically targeted malignant cells, with a 1500-fold difference in RNA delivery into tumor cells versus non-malignant cells within the tumor mass. Single-cell RNA-sequencing (scRNA-seq) and flow cytometry demonstrated that TMAB3/3p-hpRNA treatment elicited anti-tumoral immune responses against tumor cells. These studies establish that TMAB3/3p-hpRNA complexes can effectively deliver RNA payloads to malignant cells in hard-to-treat tumors to achieve anti-tumor efficacy, providing an antibody-based platform to advance RNA therapies for cancer.

ORGANISM(S): Mus musculus

PROVIDER: GSE291254 | GEO | 2025/03/14

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

A tumor suppressive-molecular axis EP300/circRERE/miR-6837-3p/MAVS activates type I interferon pathway and anti-tumor immunity to suppress colorectal cancer

Project description:Purpose: The oncogenic role of circRNAs has been well-studied in cancers including colorectal cancer (CRC). However, tumor-suppressive circRNAs and the mechanism through which they exert their anti-tumor effects remain largely unknown. We aim to find out the critical tumor-suppressive circRNAs and their possibility to serve as gene therapy targets. Experimental Design: CircRNA sequencing, gain- and loss- of function experiments，and transcriptomic analysis were performed to find tumor-suppressive and anti-tumor immunity effects of circRERE. Molecular biology experiments were conducted for mechanism exploration. Finally, we conducted adeno-associated virus to deliver circRERE (circRERE-AAV) and evaluated circRERE-AAV alone and in combination with anti-PD-1 antibody in C57BL/6J mice bearing subcutaneous MC38 tumors. Results: CircRERE is lowly expressed in CRC and its lower expression predicts worse prognosis of CRC patients in clinic. Overexpression of circRERE inhibits the malignant behaviors of CRC in vitro and in vivo, while knockdown exhibits the opposite effects. The expression of circRERE is regulated by EP300, a histone acetyltransferase downregulated in CRC as well. Mechanistically, circRERE acts as a ceRNA to sponge miR-6837-3p to upregulate MAVS expression, thereby activating type I IFN signaling and promoting anti-tumor immunity. Delivery of circRERE-AAV elicits significant anti-tumor effects, and combination treatment with circRERE-AAV and anti-PD-1 antibody exhibits synergistic effects on tumor growth in preclinical models of CRC. Conclusions: These results uncover modulatory axis constituting of EP300/circRERE/miR-6837-3p/MAVS and its essential roles in anti-tumor immunity, and demonstrate that circRERE-AAV might represent a new therapeutic avenue to prime immune responses and boost the effects of immunotherapy in clinic.

2023-03-17 | GSE224734 | GEO

PD1-targeted cis-delivery of an IL-2 variant induces a multifaceted anti-tumoral T cell response in human lung cancer

Project description:Antibody-cytokine fusion proteins are being developed as next-generation cancer immunotherapies, aiming to deliver activation signals to targeted immune populations. Among these, PD1-IL2v - an engineered interleukin-2 variant (IL-2v) lacking CD25 binding, fused to a high affinity programmed cell death protein-1 (PD-1) blocking antibody - has shown promising results in murine tumor models. Here, using human model systems, we show that PD1-IL2v elicits a multifaceted anti-tumor T cell response by targeting both CD8⁺ and conventional CD4⁺ T cells (Tconv). Single cell RNA sequencing (scRNAseq) on a lung cancer patient-derived tumor fragment (PDTF) platform revealed that PD1-IL2v drives the expansion of proliferative, cytotoxic CD8⁺ T cells exhibiting features of tumor reactivity. This was accompanied by upregulation of CXCR6, enhancing their migratory capacity. In Tconv cells, PD1-IL2v upregulated CXCL13 expression and promoted a Tfh/Th1-like transcriptional program associated with anti-PD1 responsiveness. Our findings provide mechanistic insights into the effects of IL-2v targeted delivery to PD-1⁺ cells within human tumors, supporting the clinical development of next-generation immunocytokines.

2025-07-30 | GSE303680 | GEO

Inhibiting collagen I production and tumor cell colonization in the lung via miR-29a-3p loading of exosome-/liposome-based nanovesicles

Project description:The lung is one of the most common sites for cancer metastasis. Collagens in the lung provide a permissive microenvironment that supports the colonization and outgrowth of disseminated tumor cells. Therefore, down-regulating the production of collagens may contribute to the inhibition of lung metastasis. It has been suggested that miR-29 exhibits effective anti-fibrotic activity by negatively regulating the expression of collagens. Indeed, our clinical lung tumor data shows that miR-29a-3p expression negatively correlates with collagen I expression in lung tumors and positively correlates with patients’ outcomes. However, suitable carriers need to be selected to deliver this therapeutic miRNA to the lungs. In this study, we found that the chemotherapy drug cisplatin facilitated miR-29a-3p accumulation in the exosomes of lung tumor cells, and this type of exosomes exhibited a specific lung-targeting effect and promising collagen down-regulation. To scale up the preparation and simplify the delivery system, we designed a lung-targeting liposomal nanovesicle (by adjusting the molar ratio of DOTAP/cholesterol–miRNAs to 4:1) to carry miR-29a-3p and mimic the exosomes. This liposomal nanovesicle delivery system significantly down-regulated collagen I secretion by lung fibroblasts in vivo, thus alleviating the establishment of a pro- metastatic environment for circulating lung tumor cells.

2020-11-20 | GSE161832 | GEO

Oleuropein reprograms the immunosuppressive footprint of tumor-associated myeloid cells and enhances PD-L1/PD-1 blockade immunotherapy in cancer

Project description:Therapies based on PD-1/PD-L1 blockade fail in most cancer patients. Here we evaluated the capacities of oleuropein to reprogram tumor-associated immunosuppressive myeloid cells to increase the potency of immunotherapies. Oleuropein caused major global reprogramming of monocytic and granulocytic myeloid-derived suppressor cells and tumor-associated macrophages towards immunostimulatory subsets. Differential quantitative proteomics uncovered activated and down-modulated pathways at high resolution for each subset which regulated major differentiation programs. Oleuropein significantly potentiated the capacities of myeloid cells to activate T-cells and enhanced antitumor properties of PD-1 blockade, either by systemic anti-PD-1 antibody administration, or locally by intratumor antibody delivery with a self-amplifying RNA vector based on Semliki Forest virus. Combination therapies decreased tumor infiltration by immunosuppressive myeloid cells and increased dendritic cell recruitment within draining lymph nodes, leading to systemic antitumor T-cell responses. Potent therapeutic activities were evident in lung cancer models resistant to immunotherapies and in colon cancer models.

2024-12-08 | PXD047616 | JPOST Repository

Oxaliplatin-Induced Upregulation of Exosomal miR-424-3p Derived from Human Bone Marrow Mesenchymal Stem Cells Attenuates Progression of Gastric Cancer Cells

Project description:Introduction Chemotherapy, particularly with oxaliplatin, is a key treatment for advanced gastric cancer (GC), and exosomes derived from human bone marrow mesenchymal stem cells (hBM-MSCs) play a vital role in the tumor microenvironment. Objectives The study aims to elucidate the previously unexplored role of exosomes derived from hBM-MSCs in GC tumorigenesis, especially under the influence of chemotherapy. Methods We conducted an integrated study, utilizing miRNA sequencing and biological experiments, to analyze the tumorigenicity of exosomal miR-424-3p secreted by hBM-MSCs and its target gene RHOXF2 in GC cell lines. The results were confirmed through experimentation using a xenograft mouse model. Results This study demonstrated the role of hBM-MSCs in the GC microenvironment, focusing on their Epithelial-Mesenchymal Transition (EMT) facilitation through exosomes, which led to enhanced tumorigenicity of in GC cells. Intriguingly, this pro-tumor effect was abrogated when hBM-MSCs were treated with oxaliplatin. Exosomal miRNA sequencing revealed that oxaliplatin can upregulate the levels of miR-424-3p in exosomes secreted by hBM-MSCs, thereby inhibiting the EMT process in GC cells. Furthermore, miR-424-3p was identified to target and downregulate RHOXF2 expression, impeding the malignant behavior of GC cells both in vitro and in the mouse model. Conclusions These findings uncover a potential hidden mechanism of oxaliplatin's anti-tumor action and propose the delivery of miR-424-3p via exosomes as a promising avenue for anti-tumor therapy.

2023-11-30 | GSE248357 | GEO

Impact of B16F0 exosomes on the transcriptome of CTLL2 cytotoxic T cells

Project description:While recent clinical studies demonstrate the promise of cancer immunotherapy, a barrier for broadening the clinical benefit is identifying how tumors locally suppress cytotoxic immunity. As an emerging mode of intercellular communication, exosomes secreted by malignant cells can deliver a complex payload of coding and non-coding RNA to cells within the tumor microenvironment. Here, we quantified the RNA payload within tumor-derived exosomes and the resulting dynamic transcriptomic response to cytotoxic T cells upon exosome delivery to better understand how tumor-derived exosomes can alter immune cell function. Exosomes derived from B16F0 melanoma cells were enriched for a subset of coding and non-coding RNAs that did not reflect the abundance in the parental cell. Upon exosome delivery, RNAseq revealed the dynamic changes in the transcriptome of CTLL2 cytotoxic T cells. In analyzing transiently co-expressed gene clusters, pathway enrichment suggested that the B16F0 exosomal payload altered mitochondrial respiration, which was confirmed independently, and upregulated genes associated with the Notch signaling pathway. Interestingly, exosomal miRNA appeared to have no systematic effect on downregulating target mRNA levels.

2018-03-13 | GSE103000 | GEO

Tumor-activating IL2 rejuvenates intratumoral TIM3-CD8+T cell responses through targeting TIM3+CD8+T cell

Project description:TIM3, a T-cell inhibitory receptor, is expressed on exhausted T cells in tumor microenvironment (TME). Anti-TIM3 antibody therapy could alleviate the suppression of tumor-infiltrating lymphocytes (TILs) in IL-2 dependent fashion. We hypothesize that high expression of TIM3 and limited IL-2 in TME facilitate immune evasion. To test that, we engineered anti-TIM3-pro-IL2 to selectively deliver IL-2 to TIM3high TILs by TIM3 antibody and reduce its toxicity with a cis delivery mechanism. Since IL-2 could reduce its activity at acidic pH inside TME, we also screened a low pH-selective IL-2 mutein (IL2V2) with enhanced affinity for IL-2Rβ. We then integrated pro-IL-2 into the anti-TIM3 antibodies in two different forms: TIM3-Rα-MMPs-IL2V2 (TIM3-ProIL2V2) as IL-2 release-form vs TIM3-IL2V2-MMPs-Rα as cis-form after binding to TIM3high T cells, ensuring the need of targeted delivery to TIM3-expressing TILs. Surprisingly, released IL2V2 from TIM3-Rα-MMPs-IL2V2 proved superior in anti-tumor immunity, but not cis delivery form TIM3-IL2V2-MMPs-Rα. Mechanistically, TIM3-ProIL2V2 not only reactivated TIM3+ TILs but also facilitated the activation and expansion of TIM3- T cells which in turn supported a sustained source of TIM3+ effector. TIM3-ProIL2V2 could control multiple tumor models including human tumor in humanized mice, confirming the hypothesis. TIM3-ProIL2V2 activates and expands TIM3-CD8+ T cells to overcome current major unmet medical need: anti-PD-1/L1 resistance. This strategy illustrates the potential of a tailored, low pH-resistant IL2 variant in invigorating both TIM3-negative and positive CD8+ T cells, offering a promising avenue for treating resistant tumors with reduced toxicity.

2025-05-22 | GSE296919 | GEO

Pancreatic tumor microenvironment confers highly malignant properties on pancreatic cancer cells

Project description:Tumor microenvironment plays a pivotal role in cancer progression; however, little is known regarding how differences in the microenvironment affect characteristics of cancer cells. Here, we investigated the effects of tumor microenvironment on cancer cells by using mouse tumor models. After 3 cycles of inoculation and extraction of human pancreatic cancer cells, including SUIT-2 and Panc-1 cells, from tumors, distinct cancer cell lines were established; 3P cells from the pancreas obtained using the orthotopic tumor model, and 3sc cells from subcutaneous tissue obtained using the subcutaneous tumor model. On cell re-inoculation of these cells, the 3sc cells and, more prominently, the 3P cells, exhibited higher tumorigenic activity than the parental cells. The 3P cells specifically exhibited low E-cadherin expression and high invasiveness, suggesting that they were endowed with the highest malignant characteristics. RNA-sequence analysis demonstrated that distinct signaling pathways were activated in each cell line and that the 3P cells acquired a cancer stem cell-like phenotype. Among cancer stem cell-related genes, those specifically expressed in the 3P cells, including NES, may be potential new targets for cancer therapy. The mechanisms underlying the development of highly malignant cancer cell lines were investigated. Individual clones within the parental cells varied in tumor-forming ability, indicating the presence of cellular heterogeneity. Moreover, the gene expression profile of each clone changed after orthotopic inoculation. The present study thus suggests that both selection and education processes are involved in the development of highly malignant cancer cells.

2018-03-12 | GSE107960 | GEO

Using an RNA-binding antibody for tumor-directed immunogenic RNA delivery

Project description:Using an RNA-binding antibody for tumor-directed immunogenic RNA delivery

| PRJNA1232670 | ENA

Programmable envelopved delivery vehicels for human genome engineering in vivo

Project description:Viruses and virally-derived particles have the intrinsic capacity to deliver molecules to cells, but the difficulty of readily altering cell-type selectivity has hindered their use for therapeutic delivery. Here we show that cell surface marker recognition by antibody fragments displayed on membrane-derived particles encapsulating CRISPR-Cas9 protein and guide RNA can target genome editing tools to specific cells. These Cas9-packaging enveloped delivery vehicles (Cas9-EDVs), programmed with different displayed antibody fragments, confer genome editing in target cells over bystander cells in mixed cell populations both ex vivo and in vivo. This strategy enabled the generation of genome-edited chimeric antigen receptor (CAR) T cells in humanized mice, establishing a new programmable delivery modality with the potential for widespread therapeutic utility.

2023-06-30 | GSE235643 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data