Mechanism of cell death induced by saporin
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE42138 | GEO | 2012/11/09
SECONDARY ACCESSION(S): PRJNA179198
REPOSITORIES: GEO
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Project description:Insights into the mechanism of cell death induced by saporin delivered into cancer cells by an antibody fusion protein targeting the transferrin receptor 1 These studies detail transcriptional changes induced in cancer cells by the complex of saporin (b-SO6) and the antibody fusion protein ch128.1Av. Delivery of saporin into cancer cells by ch128.1Av, induces a transcriptional response consistent with oxidative stress and DNA damage, a response that is not observed with ch128.1Av alone. Time course, after delivery of saporin into cells by ch128.1Av
2012-11-09 | E-GEOD-42138 | biostudies-arrayexpress
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Project description:The use of lipid nanoparticles (LNP) to encapsulate and deliver mRNA has become an important therapeutic advance. In addition to vaccines, LNP-mRNA can be used in many other applications. For example, targeting the LNP with anti-CD5 antibodies (CD5/tLNP) can allow for efficient delivery of mRNA payloads to T cells to express protein. As the percentage of protein expressing T cells induced by an intravenous injection of CD5/tLNP is relatively low (4-20%), our goal was to find ways to increase mRNA-induced translation efficiency. We showed that T cell activation using an anti-CD3 antibody improved protein expression after CD5/tLNP transfection in vitro but not in vivo. T cell health and activation can be increased with cytokines, therefore, using mCherry mRNA as a reporter, we found that culturing either mouse or human T cells with the cytokine IL7 significantly improved protein expression of delivered mRNA in both CD4+ and CD8+ T cells in vitro. By pre- treating mice with systemic IL7 followed by tLNP administration, we observed significantly increased mCherry protein expression by T cells in vivo. Transcriptomic analysis of mouse T cells treated with IL7 in vitro revealed enhanced genomic pathways associated with protein translation. Improved translational ability was demonstrated by showing increased levels of protein expression after electroporation with mCherry mRNA in T cells cultured in the presence of IL7, but not with IL2 or IL15. These data show that IL7 selectively increases protein translation in T cells, and this property can be used to improve expression of tLNP-delivered mRNA in vivo.
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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.
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