Immunotherapy for breast cancer using EpCAM aptamer tumor-targeted gene knockdown efficacy
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ABSTRACT:
PROVIDER: PRJNA657057 | ENA |
REPOSITORIES: ENA
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Project description:New strategies for cancer immunotherapy are needed since most solid tumors do not respond to current approaches. Here, we used EpCAM aptamer-linked small interfering RNAs (aptamer-siRNA chimeras (AsiCs)) to knockdown genes selectively in EpCAM+ tumors with the goal of making cancers more visible to the immune system to improve anti-tumor immunity. Gene targets were chosen whose knockdown was predicted to promote tumor neoantigen expression (Upf2 and Parp1), phagocytosis and antigen presentation (Cd47), or cause tumor cell death (Mcl1). Using scRNA-seq, we showed that knocking down the four targets simutaeoulsy potently improved the anti-tumor immunity mediated T cells and macrophage/monocytes, demonstrating the immunostimulatory capacity of EpCAM-AsiCs.
2021-02-05 | GSE156214 | GEO
Project description:siRNAs have played a major role in cancer drug discovery, but their potential is hampered due to off-target effects. Thus, delivery systems like RNA aptamers have been used to enhance the specific delivery of these siRNAs to cancer stem cells. We report the efficacy of three different EpCAM aptamer siRNA chimeras, which were investigated both in vitro and in vivo for their ability to reduce cancer cell progression. Using these chimeras, we demonstrated specific gene knockdown in EpCAM positive cells which ultimately led to the apoptosis. To study the efficacy of these aptamer chimeras in vivo, retinoblastoma xenografts bearing NCC Rb C 51 cells were created for the first time. Systemic administration of these aptamer chimeras reduced tumour growth to about 50%. We further investigated the central Role of PLK1 in Cancer Progression and demonstrated the anti-cancer effects of targeted EpCAM siPLK1 approach. Using SILAC-Mass spectrometry analysis, we showed that silencing PLK 1 gene can lead to p53 mediated cell cycle arrest. Thus, we establish EpCAM-siRNA chimeras as potential markers for targeted anti-cancer applications, which paves a platform for efficient second line of therapies in addition to existing chemotherapy options.
2022-03-02 | PXD008221 | Pride
Project description:Neocarzinostatin (NCS) is an anti-tumor DNA damaging agent. Conjugating NCS with EpCAM Aptamer will direct the toxin pay loads to the EpCAM positive cancer cells as a targeted therapy We used microarrays to detail the global gene expression to understand the pathways involved in EpCAM-mediated NCS drug delivery in breast cancer cells.
2018-09-05 | GSE69160 | GEO
Project description: Not available
| S-EPMC7936362 | biostudies-literature
Project description:Immunotherapy for breast cancer using EpCAM aptamer tumor-targeted gene knockdown efficacy_UPF2 knockdown in EpCAMhi MDA-MB-231 breast cancer cell lines
| PRJNA657010 | ENA
Project description:Saporin (SAP) is an Ribosomal inactivation protein (RIP) toxin molecule. Conjugating SAP with EpCAM Antibody will direct the toxin pay loads to the EpCAM positive cancer cells as a targeted therapy We used microarrays to detail the global gene expression to understand the pathways involved in EpCAM-mediated SAP drug delivery in breast cancer cells.
2018-09-05 | GSE70745 | GEO
Project description:Knocking down Upf2, which encodes a protein that binds to prematurely terminated mRNAs to activate NMD, has been postulated to induce tumor cell expression of neoantigens to promote tumor recognition by T cells. To investigate whether Upf2 knockdown in breast cancer generates novel mRNA isoforms, we performed bulk RNA sequencing (RNA-seq) to compare an EpCAMhi MDA-MB-231 human breast cancer cell line transfected with noncoding control or UPF2 siRNA for 72 h. Results: 222 examples of differential exon usage (DEU) within 281 genes were identified. The number and diversity of DEUs suggest that UPF2 knockdown could have caused novel alternative splicing. To test this idea, UPF2 knockdown-related transcriptional diversity was deconvoluted to identify and estimate the abundance of transcript isoforms. 42 genes with potential differential isoform usage (DIU) were identified. Collectively, our data suggest that reducing NMD activity by UPF2 knockdown may induce expression of tumor neoantigens.
2021-02-05 | GSE156185 | GEO
Project description:The experiments were carried out to map the ligand binding landscape of various DNA and RNA duplexed aptamer families. Duplexed Aptamer (DA) constructs were engineered from (i) natural and synthetic DNA and RNA aptamers and (i) synthetic oligonucleotide aptamer-complementary elements synthesized on custom DNA microarrays. The aptamers tested consist of the ATP DNA aptamer, the ATP RNA aptamer, the cocaine DNA aptamer, the human alpha-thrombin DNA aptamer, and the natural add riboswitch aptamer from the pathogenic bacteria Vibrio vulnificus. Each duplexed aptamer family consists of 1000's of synthetic constructs, each formed by hybridizing the aptamer with an aptamer-complementary element (ACE) - here, ACEs consisted of various DNA oligonucleotides synthesized as a custom DNA microarray.
2017-12-20 | E-MTAB-6377 | biostudies-arrayexpress
Project description:The experiments were carried out to map the ligand binding landscape of various DNA and RNA duplexed aptamer families. Duplexed Aptamer (DA) constructs were engineered from (i) natural and synthetic DNA and RNA aptamers and (i) synthetic oligonucleotide aptamer-complementary elements synthesized on custom DNA microarrays. The aptamers tested consist of the ATP DNA aptamer, the ATP RNA aptamer, the cocaine DNA aptamer, the human alpha-thrombin DNA aptamer, and the natural add riboswitch aptamer from the pathogenic bacteria Vibrio vulnificus. Each duplexed aptamer family consists of 1000's of synthetic constructs, each formed by hybridizing the aptamer with an aptamer-complementary element (ACE) - here, ACEs consisted of various DNA oligonucleotides synthesized as a custom DNA microarray.
2017-12-20 | E-MTAB-6375 | biostudies-arrayexpress
Project description:The experiments were carried out to map the ligand binding landscape of various DNA and RNA duplexed aptamer families. Duplexed Aptamer (DA) constructs were engineered from (i) natural and synthetic DNA and RNA aptamers and (i) synthetic oligonucleotide aptamer-complementary elements synthesized on custom DNA microarrays. The aptamers tested consist of the ATP DNA aptamer, the ATP RNA aptamer, the cocaine DNA aptamer, the human alpha-thrombin DNA aptamer, and the natural add riboswitch aptamer from the pathogenic bacteria Vibrio vulnificus. Each duplexed aptamer family consists of 1000's of synthetic constructs, each formed by hybridizing the aptamer with an aptamer-complementary element (ACE) - here, ACEs consisted of various DNA oligonucleotides synthesized as a custom DNA microarray.
2017-12-20 | E-MTAB-6376 | biostudies-arrayexpress