Combinatorial targeting of cancer bone metastasis using mRNA engineered stem cells

Ségaliny, Aude I.; Cheng, Jason L.; Farhoodi, Henry P.; Toledano, Michael; Yu, C. C.; Tierra, Beatrice; Hildebrand, Leanne; Liu, Linan; Liao, Michael J.; Cho, Jaedu; Li, Dongxu; Sun, Lizhi; Gülşen, Gültekin; Su, Min–Ying; Sah, Robert L.; Zhao, Weian

doi:10.1016/j.ebiom.2019.06.047

Cited by 18 publications

(9 citation statements)

References 77 publications

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“…Engineered MSCs were mostly used to treat tumor/cancer/ malignancy/metastasis (51 studies, Supplementary Table 1), and the rest of the studies reported the use of engineered MSCs to treat various non-tumor conditions (34 studies, Supplementary Table 2). MSCs from several different sources and species were used in the reviewed papers, i.e., human bone marrow (BM) MSCs (Sasportas et al, 2009;You et al, 2009;Gao et al, 2010;Wang et al, 2012;Altaner et al, 2014;Harati et al, 2015;NguyenThai et al, 2015;Nouri et al, 2015;Beegle et al, 2016;Chung et al, 2016;Schug et al, 2018;Segaliny et al, 2019), human adipose tissue (AT) MSCs (Kucerova et al, 2007(Kucerova et al, , 2008(Kucerova et al, , 2014Cavarretta et al, 2010;Altanerova et al, 2012;Zolochevska et al, 2012;Altaner et al, 2014;Grisendi et al, 2015;Matuskova et al, 2015;Tyciakova et al, 2015;Toro et al, 2016;Roudkenar et al, 2018), rat BM-MSCs (Tsuchida et al, 2003;Li et al, 2007;Jiang et al, 2009;Huang et al, 2010;Zhang et al, 2010Zhang et al, , 2011Zhao et al, 2010;Fei et al, 2012;Kosaka et al, 2012;Kim et al, 2013;Nakamura et al, 2013;Hu et al, 2014;Niu et al, 2014;…”

Section: Resultsmentioning

confidence: 99%

Enhancement of the Therapeutic Capacity of Mesenchymal Stem Cells by Genetic Modification: A Systematic Review

Pawitan

Bui

Mubarok

et al. 2020

Front. Cell Dev. Biol.

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Background: The therapeutic capacity of mesenchymal stem cells (also known as mesenchymal stromal cells/MSCs) depends on their ability to respond to the need of the damaged tissue by secreting beneficial paracrine factors. MSCs can be genetically engineered to express certain beneficial factors. The aim of this systematic review is to compile and analyze published scientific literatures that report the use of engineered MSCs for the treatment of various diseases/conditions, to discuss the mechanisms of action, and to assess the efficacy of engineered MSC treatment. Methods:We retrieved all published studies in PubMed/MEDLINE and Cochrane Library on July 27, 2019, without time restriction using the following keywords: "engineered MSC" and "therapy" or "manipulated MSC" and "therapy." In addition, relevant articles that were found during full text search were added. We identified 85 articles that were reviewed in this paper.Results: Of the 85 articles reviewed, 51 studies reported the use of engineered MSCs to treat tumor/cancer/malignancy/metastasis, whereas the other 34 studies tested engineered MSCs in treating non-tumor conditions. Most of the studies reported the use of MSCs in animal models, with only one study reporting a trial in human subjects. Thirty nine studies showed that the expression of beneficial paracrine factors would significantly enhance the therapeutic effects of the MSCs, whereas thirty three studies showed moderate effects, and one study in humans reported no effect. The mechanisms of action for MSC-based cancer treatment include the expression of "suicide genes," induction of tumor cell apoptosis, and delivery of cytokines to induce an immune response against cancer cells. In the context of the treatment of non-cancerous

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Section: Resultsmentioning

confidence: 99%

Enhancement of the Therapeutic Capacity of Mesenchymal Stem Cells by Genetic Modification: A Systematic Review

Pawitan

Bui

Mubarok

et al. 2020

Front. Cell Dev. Biol.

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“…Moreover, RANKL produced by both breast cancer cells and osteoblast further stimulates osteoclast differentiation and activity-binding RANK on the cell surface [50,51]. In contrast, osteoblasts secrete osteoprotegerin (OPG), a soluble decoy receptor for RANKL, which inhibits RANK/RANKL signaling negatively regulating osteoclastogenesis [52][53][54]. Of note, osteoclast differentiation may also be elicited by IL6, IL1, prostaglandins, and M-CSF-mediated stimulation of bone marrow macrophages [25,55,56].…”

Section: Biological Mechanisms Of Bone Metastasismentioning

confidence: 99%

Breast Cancer with Bone Metastasis: Molecular Insights and Clinical Management

Venetis

Piciotti

Sajjadi

et al. 2021

Cells

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Despite the remarkable advances in the diagnosis and treatment of breast cancer patients, the presence or development of metastasis remains an incurable condition. Bone is one of the most frequent sites of distant dissemination and negatively impacts on patient’s survival and overall frailty. The interplay between tumor cells and the bone microenvironment induces bone destruction and tumor progression. To date, the clinical management of bone metastatic breast cancer encompasses anti-tumor systemic therapies along with bone-targeting agents, aimed at slowing bone resorption to reduce the risk of skeletal-related events. However, their effect on patients’ survival remains controversial. Unraveling the biology that governs the interplay between breast neoplastic cells and bone tissue would provide means for the development of new therapeutic agents. This article outlines the state-of-the art in the characterization and targeting the bone metastasis in breast cancer, focusing on the major clinical and translational studies on this clinically relevant topic.

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“…In developing this CAR-based anticancer strategy, we aimed to reach site-specific and lasting retention of MSCs within the tumor bed, thereby effectively delivering proapoptotic TRAIL molecules to GD2-expressing tumors (Golinelli et al, 2018). Combinatorial targeting has recently been applied by Segaliny and colleagues, who produced MSCs that express P-selectin glycoprotein ligand-1 (PSGL-1)/Sialyl-Lewis X (SLEX) together with modified versions of CD and osteoprotegerin (OPG) to treat bone metastases of breast cancer (Segaliny et al, 2019). MSC delivery to bones has been improved through interactions between PSGL-1/SLEX and selectins on activated endothelial cells, megakaryocytes, and platelets in the tumor microenvironment.…”

Section: Improving Msc Tumor Targetingmentioning

confidence: 99%

“…MSC delivery to bones has been improved through interactions between PSGL-1/SLEX and selectins on activated endothelial cells, megakaryocytes, and platelets in the tumor microenvironment. Once in the tumor niche, engineered MSCs induced local cancer killing through a CD/5-FC suicide gene therapy system and reduced osteolysis by expressing modified OPG (Segaliny et al, 2019). Also noteworthy is the technology developed by Zhu et al aimed at simultaneously targeting cell proliferation and death pathways in tumor cells using MSCs armed with a bi-functional molecule comprised of a nanobody targeting the EGFR (Enb) and TRAIL (Zhu et al, 2017).…”

Section: Improving Msc Tumor Targetingmentioning

confidence: 99%

Section: Improving Msc Tumor Targetingmentioning

confidence: 99%

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Arming Mesenchymal Stromal/Stem Cells Against Cancer: Has the Time Come?

et al. 2020

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Since mesenchymal stromal/stem cells (MSCs) were discovered, researchers have been drawn to study their peculiar biological features, including their immune privileged status and their capacity to selectively migrate into inflammatory areas, including tumors. These properties make MSCs promising cellular vehicles for the delivery of therapeutic molecules in the clinical setting. In recent decades, the engineering of MSCs into biological vehicles carrying anticancer compounds has been achieved in different ways, including the loading of MSCs with chemotherapeutics or drug functionalized nanoparticles (NPs), genetic modifications to force the production of anticancer proteins, and the use of oncolytic viruses. Recently, it has been demonstrated that wild-type and engineered MSCs can release extracellular vesicles (EVs) that contain therapeutic agents. Despite the enthusiasm for MSCs as cyto-pharmaceutical agents, many challenges, including controlling the fate of MSCs after administration, must still be considered. Preclinical results demonstrated that MSCs accumulate in lung, liver, and spleen, which could prevent their engraftment into tumor sites. For this reason, physical, physiological, and biological methods have been implemented to increase MSC concentration in the target tumors. Currently, there are more than 900 registered clinical trials using MSCs. Only a small fraction of these are investigating MSC-based therapies for cancer, but the number of these clinical trials is expected to increase as technology and our understanding of MSCs improve. This review will summarize MSC-based antitumor therapies to generate an increasing awareness of their potential and limits to accelerate their clinical translation.

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Combinatorial targeting of cancer bone metastasis using mRNA engineered stem cells

Cited by 18 publications

References 77 publications

Enhancement of the Therapeutic Capacity of Mesenchymal Stem Cells by Genetic Modification: A Systematic Review

Enhancement of the Therapeutic Capacity of Mesenchymal Stem Cells by Genetic Modification: A Systematic Review

Breast Cancer with Bone Metastasis: Molecular Insights and Clinical Management

Arming Mesenchymal Stromal/Stem Cells Against Cancer: Has the Time Come?

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