Targeted Delivery of CX3CL1 to Multiple Lung Tumors by Mesenchymal Stem Cells

Xin, Hong; Kanehira, Masafumi; Mizuguchi, Hiroyuki; Hayakawa, Tetsuo; Kikuchi, Toshiaki; Nukiwa, Toshihiro; Saijo, Yasuo

doi:10.1634/stemcells.2006-0461

Cited by 153 publications

(105 citation statements)

References 36 publications

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“…This tropism has been exploited to deliver multiple therapeutic genes or cDNAs selectively to tumor foci (summarized in Table 1; stem and progenitor cells for tumor-selective therapy). 3,10,[15][16][17][23][24][25][26][27][28][29][30][31] The central question to be addressed then becomes whether we can exploit the inherent ability of these cells to migrate to, infiltrate and-when desirable-engraft to 'correct' pathologies in patients. The long-range goal is complete cure without toxic side effects or relapse.…”

Section: Introductionmentioning

confidence: 99%

Stem and progenitor cell-mediated tumor selective gene therapy

2008

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The poor prognosis for patients with aggressive or metastatic tumors and the toxic side effects of currently available treatments necessitate the development of more effective tumor-selective therapies. Stem/progenitor cells display inherent tumor-tropic properties that can be exploited for targeted delivery of anticancer genes to invasive and metastatic tumors. Therapeutic genes that have been inserted into stem cells and delivered to tumors with high selectivity include prodrug-activating enzymes (cytosine deaminase, carboxylesterase, thymidine kinase), interleukins (IL-2, IL-4, IL-12, IL-23), interferon-b, apoptosis-promoting genes (tumor necrosis factor-related apoptosis-inducing ligand) and metalloproteinases (PEX). We and others have demonstrated that neural and mesenchymal stem cells can deliver therapeutic genes to elicit a significant antitumor response in animal models of intracranial glioma, medulloblastoma, melanoma brain metastasis, disseminated neuroblastoma and breast cancer lung metastasis. Most studies reported reduction in tumor volume (up to 90%) and increased survival of tumor-bearing animals. Complete cures have also been achieved (90% disease-free survival for 41 year of mice bearing disseminated neuroblastoma tumors). As we learn more about the biology of stem cells and the molecular mechanisms that mediate their tumor-tropism and we identify efficacious gene products for specific tumor types, the clinical utility of cell-based delivery strategies becomes increasingly evident.

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Section: Introductionmentioning

confidence: 99%

Stem and progenitor cell-mediated tumor selective gene therapy

2008

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“…No toxicities were observed and an increased apoptotic index and reduction in lymphatic sprouting were also found [50]. In C26 colon and B16F10 melanoma mouse models, chemokine (C-X3-C-motif) ligand 1-expressing-MSCs reduced metastatic nodules and resulted in longer survival [51]. MSCs engineered to secrete interferon-β suppressed growth of breast, prostate, pancreatic and melanoma cancers in animal models [52][53][54][55], as did interleukin-12-expressing MSCs in renal cell cancer [56].…”

Section: The Promise Of Mscs In Cancer Therapymentioning

confidence: 92%

Mesenchymal Stem Cells: How Can we Realize their Therapeutic Potential in Cancer Therapy?

Baird

2015

J Clin Exp Pathol

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Mesenchymal stem cells home to the tumour stroma from the bone marrow, influencing early tumour development and metastasis. Mesenchymal stem cells have been shown to be promising vehicles for cancer therapy due to this tropism for tumour sites, their immunoprivileged status, easy extraction from bone marrow and facile transfection. Mesenchymal stem cells have been used to deliver gene therapy in the form of cytokines or adenovirus and as part of prodrug strategies. However, in order for these agents to be tested in clinical trials, the biology of mesenchymal stem cells must be further investigated. At present there is variation between research groups surrounding mesenchymal stem cell isolation and characterisation methods, as well as in how the cells are delivered to in vivo models, making studies hard to compare. Research examining the attraction of mesenchymal stem cells to tumours has found that the cells home towards a wide range of growth factors, cytokines and proteases. Once part of the tumour stroma, mesenchymal stem cells may have both pro-and anti-tumorigenic effects, increasing tumour growth, angiogenesis and metastasis and decreasing immune activation in some systems, and in others, reducing tumour cell proliferation and development of metastases. Understanding more precisely which subsets of mesenchymal stem cells support or undermine the development of the tumour at various timepoints will enable an effective clinical trial strategy for mesenchymal stem cell-based cancer therapies to be developed and replicated with different cancers and treatment sites.

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“…Therapeutic proteins which raised great interest because of the possibility to be managed by MSCs are interferon (IFN ) [31,32] and (IFN ) [23,[31][32][33][34], interleukin (IL) 12 [35], cytokine IL2 [36] and chemokine CX3CL1 (fractalkine) [37]. There are a number of studies of effects of IFN and IFN incorporated into systems delivered by MSCs over tumor growth showing the inhibitory effect of IFN and its usefulness as adjuvant therapy for the elimination of micrometastasis in risk patients [38], while anticancer effect of IFN is determined as apoptosis-stimulation effect [39,40] and only toxicity observed after its systemic administration limits its clinical applications [41].…”

Section: Mscs Engineered As Anticancer Drug De-livery Systemsmentioning

confidence: 99%

Perspectives in Engineered Mesenchymal Stem/Stromal Cells Based Anti- Cancer Drug Delivery Systems

Ackova¹,

Kanjevac²,

Rimondini³

et al. 2016

PRA

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Understanding and apprehension of the characteristics and circumstances in which mesenchymal stem cells (MSCs) affect and make alterations (enhance or reduce) to the growth of tumors and metastasis spread is pivotal, not only for reaching the possibility to employ MSCs as drug delivery systems, but also for making forward movement in the existing knowledge of involvement of major factors (tumor microenvironment, soluble signaling molecules, etc.) in the process of carcinogenesis. This capability is reliable because MSCs present a great basis for engineering and constructions of new systems to target cancers, intended to secrete therapeutic proteins in the tumor region, or for delivering of oncolytic viruses' directly at the tumor site (targeted chemotherapy with enzyme prodrug conversion or induction of tumor cell apoptosis). MSCs as a crucial segment of the tumor surroundings and their confirmed tumor tropism, are assumed to be an open gateway for the design of promising drug delivery systems. The presented paper reviews current publications in this fieldwork, searches out the most recent patents that were published after 2012 (WO2014066122, US20140017787, WO2015100268, US20150086515), and tries to present the current progress and future prospective on the design and development in anti-cancer drug delivery systems based on MSCs.

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Targeted Delivery of CX3CL1 to Multiple Lung Tumors by Mesenchymal Stem Cells

Abstract: ABSTRACT

Cited by 153 publications

References 36 publications

Stem and progenitor cell-mediated tumor selective gene therapy

Stem and progenitor cell-mediated tumor selective gene therapy

Mesenchymal Stem Cells: How Can we Realize their Therapeutic Potential in Cancer Therapy?

Perspectives in Engineered Mesenchymal Stem/Stromal Cells Based Anti- Cancer Drug Delivery Systems

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