dc.contributor.author |
Kaban, K |
|
dc.contributor.author |
Hinterleitner, C |
|
dc.contributor.author |
Zhou, YJ |
|
dc.contributor.author |
Salva, E |
|
dc.contributor.author |
Kantarci, AG |
|
dc.contributor.author |
Salih, HR |
|
dc.contributor.author |
Marklin, M |
|
dc.date.accessioned |
2022-10-11T12:54:59Z |
|
dc.date.available |
2022-10-11T12:54:59Z |
|
dc.date.issued |
2021 |
|
dc.identifier.uri |
http://hdl.handle.net/11616/74755 |
|
dc.description.abstract |
Simple Summary |
|
dc.description.abstract |
Overexpression of the antiapoptotic protein BCL-2 is correlated with estrogen receptor (ER) expression in breast cancer and plays an important role for disease pathophysiology. Here, we conceptualized a novel treatment strategy by targeting ER+ breast cancer with NK cell-derived exosomes used as a carrier for BCL-2 targeted siRNAs. With this new approach, we successfully enhanced killing ability of NK cell derived exosomes by silencing of BCL-2 overexpression. |
|
dc.description.abstract |
Overexpression of the anti-apoptotic protein BCL-2 is frequently observed in multiple malignancies, including about 85% of patients with estrogen receptor positive (ER+) breast cancer. Besides being studied as a prognostic marker, BCL-2 is investigated as a therapeutic target in ER+ breast cancer. Here, we introduce a new exosome-based strategy to target BCL-2 using genetically modified natural killer (NK) cells. The NK cell line NK92MI was lentivirally transduced to express and load BCL-2 siRNAs (siBCL-2) into exosomes (NKExos) and then evaluated for its potential to treat ER+ breast cancer. Transfected NK92MI cells produced substantial levels of BCL-2 siRNAs, without substantially affecting NK cell viability or effector function and led to loading of siBCL-2 in NKExos. Remarkably, targeting BCL-2 via siBCL-2 NKExos led to enhanced intrinsic apoptosis in breast cancer cells, without affecting non-malignant cells. Together, our prototypical results for BCL-2 in breast cancer provide proof of concept for a novel strategy to utilize NKExos as a natural delivery vector for siRNA targeting of oncogenes. |
|
dc.source |
CANCERS |
|
dc.title |
Therapeutic Silencing of BCL-2 Using NK Cell-Derived Exosomes as a Novel |
|
dc.title |
Therapeutic Approach in Breast Cancer |
|