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Spatiotemporal control of gene expression in bone-marrow derived cells of the tumor microenvironment induced by MRI guided focused ultrasound
Abstract : The tumor microenvironment is an interesting target for anticancer therapies but modifying this compartment is challenging. Here, we demonstrate the feasibility of a gene therapy strategy that combined targeting to bone marrow-derived tumor microenvironment using genetically modified bone-marrow derived cells and control of transgene expression by local hyperthermia through a thermo-inducible promoter. Chimera were obtained by engraftment of bone marrow from transgenic mice expressing reporter genes under transcriptional control of heat shock promoter and inoculated sub-cutaneously with tumors cells. Heat shocks were applied at the tumor site using a water bath or magnetic resonance guided high intensity focused ultrasound device. Reporter gene expression was followed by bioluminescence and fluorescence imaging and immunohistochemistry. Bone marrow-derived cells expressing reporter genes were identified to be mainly tumor-associated macrophages. We thus provide the proof of concept for a gene therapy strategy that allows for spatiotemporal control of transgenes expression by macrophages targeted to the tumor microenvironment.
Cited literature [32 references]
https://hal-cnrs.archives-ouvertes.fr/hal-02486786
Contributor : Karine Viaud Connect in order to contact the contributor
Submitted on : Friday, February 21, 2020 - 11:05:34 AM
Last modification on : Tuesday, December 1, 2020 - 10:50:04 AM
Long-term archiving on: : Friday, May 22, 2020 - 3:04:12 PM
Contributor : Karine Viaud Connect in order to contact the contributor
Submitted on : Friday, February 21, 2020 - 11:05:34 AM
Last modification on : Tuesday, December 1, 2020 - 10:50:04 AM
Long-term archiving on: : Friday, May 22, 2020 - 3:04:12 PM
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oncotarget-06-23417.pdf
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