Abstract 1320: NanoGhost: Harnessing the power of stem cell in an off-the-shelf novel targeted nano-delivery platform
Mesenchymal stem cells (MSC) have been extensively investigated as cell carriers or cell therapies for treating a wide range of malignant and inflammatory diseases. In addition, recent studies show that MSCs' tropism to malignant and inflamed tissues as well as their immunomodulatory capacity,...
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Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2021-07, Vol.81 (13_Supplement), p.1320-1320 |
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Zusammenfassung: | Mesenchymal stem cells (MSC) have been extensively investigated as cell carriers or cell therapies for treating a wide range of malignant and inflammatory diseases. In addition, recent studies show that MSCs' tropism to malignant and inflamed tissues as well as their immunomodulatory capacity, both are largely governed by direct cell-cell interactions facilitated by membrane-bound proteins. Never the less the translation of MSCs into broadly-applicable clinical applications may face obstacles due to MSCs' susceptibility to host-induced changes, limiting their ability to deliver a long-lasting effect. Based on this knowledge we developed a scalable technology for the production of nano-vesicles from the cell membrane of MSCs. These nano-vesicles, termed Nano-Ghosts (NGs), and our data demonstrate that these NGs can be used as a cancer targeted delivery platform, effectively loaded and used to selectively deliver diverse therapeutics including biological drugs, small molecules, and nucleic acids. In several preclinical cancer models (pancreatic, NSCLAC) we have shown selective NG targeting resulting in reduction in tumor growth and prolonged survival. In this study, we extend previous data and demonstrate the ability of NGs to penetrate the BBB in a two mice models for GBM demonstrating high and specific accumulation of NGs in the tumor while no off-target inn normal brain tissue nor filtrating organs. The lethal effect of drug carrying NGs was expanded by using cytotoxic ligand derived from CTLs (TRAIL) genetically engineered on the surface of the MSC-NGs, creating a new class of NGs termed immunotherapeutic NGs (iNGs). The membrane bound TRAIL enable the iNGs to inhibit significantly mice bearing melanoma tumors, without the need of a loaded drug. Our results, clearly demonstrate the translational potential of NGs, both as targeted carriers and as novel immunomodulatory biologics, for oncological and immunological applications.
Citation Format: Marcelle Machluf, Marcelle Machluf, Shani Hamias, Lior Levii, Osnat Bohana Kashtan. NanoGhost: Harnessing the power of stem cell in an off-the-shelf novel targeted nano-delivery platform [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1320. |
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ISSN: | 0008-5472 1538-7445 |
DOI: | 10.1158/1538-7445.AM2021-1320 |