Human Bone Marrow–Derived Mesenchymal Stem Cells for Intravascular Delivery of Oncolytic Adenovirus Δ24-RGD to Human Gliomas

Yong, Raymund L.; Shinojima, Naoki; Fueyo, Juan; Gumin, Joy; Vecil, Giacomo G.; Marini, Frank C.; Bögler, Oliver; Andreeff, Michael; Lang, Frederick F.

doi:10.1158/0008-5472.can-08-3873

Cited by 221 publications

(188 citation statements)

References 37 publications

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“…After intravascular administration, MSCs loaded with Ad-Δ24RGD, but not Ad-Δ24-RGD alone, migrated to and infected intracerebral gliomas, resulting in a significant increase in survival. 113 When compared directly, both human MSCs and NSCs loaded with CRAd-S-pk7 (Table I) supported Ad replication and migration to tumors, however, loaded NSCs were significantly better than MSCs in extending survival. 111 Additional studies with CRAd-S-pk7 loaded HB1.F3 NSCs, which are currently in clinical trial, demonstrated that the infected NSCs retained their tumor homing, supported Ad replication, and gave rise to infected tumor cells in vivo.…”

Section: Stem Cells As Oncolytic Virus Carriersmentioning

confidence: 98%

“…110 Several groups have demonstrated that MSCs and NSCs can support Ad infection and replication. [111][112][113][114] An advantage of this approach to oncolytic virus alone is that stem cells can be delivered intravascularly, evading anti-viral immunity, and then extravasate into the brain, or intracranially at a distance from the tumor. After intravascular administration, MSCs loaded with Ad-Δ24RGD, but not Ad-Δ24-RGD alone, migrated to and infected intracerebral gliomas, resulting in a significant increase in survival.…”

Section: Stem Cells As Oncolytic Virus Carriersmentioning

confidence: 99%

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Current Status of Gene Therapy for Brain Tumors∗

Ning

Rabkin

2015

Translating Gene Therapy to the Clinic

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Glioblastoma (GBM) is the most common and deadliest primary brain tumor in adults, with current treatments having limited impact on disease progression. Therefore the development of alternative treatment options is greatly needed. Gene therapy is a treatment strategy that relies on the delivery of genetic material, usually transgenes or viruses, into cells for therapeutic purposes, and has been applied to GBM with increasing promise. We have included selectively replicationcompetent oncolytic viruses within this strategy, although the virus acts directly as a complex biologic anti-tumor agent rather than as a classic gene delivery vehicle. GBM is a good candidate for gene therapy because tumors remain locally within the brain and only rarely metastasize to other tissues; the majority of cells in the brain are post-mitotic, which allows for specific targeting of dividing tumor cells; and tumors can often be accessed neurosurgically for administration of therapy. Delivery vehicles used for brain tumors include nonreplicating viral vectors, normal adult stem/progenitor cells, and oncolytic viruses. The therapeutic transgenes or viruses are typically cytotoxic or express prodrug activating suicide genes to kill glioma cells, immunostimulatory to induce or amplify anti-tumor immune responses, and/or modify the tumor microenvironment such as blocking angiogenesis. This review describes current preclinical and clinical gene therapy strategies for the treatment of glioma.Treating malignant gliomas, of which glioblastoma (GBM) is the most common and least curable, remains a daunting challenge even after substantial efforts to develop alternative therapies. The current standard of care is maximal surgical resection followed by radiation and temozolomide chemotherapy; however, the median survival still remains less than 15 months. 1,2 This poor survival is due to the aggressive and invasive nature of the tumor cells, resistance to treatment, and the challenges of delivering therapeutics into the brain. 3 GBM is thought to be derived from a small population of glioblastoma stem cells (GSCs), so-called because of their stem cell-like properties of self-renewal and multilineage differentiation while being highly tumorigenic. [4][5][6] GSCs have become an important model for studying GBM because their xenografts mimic the heterogeneous histopathology of the patient's tumor from which they were derived 7,8 and they remain genotypically similar to the patient's tumor, in contrast to serum-cultured cell lines. 9 These cells have provided insights into the origin of tumor-initiating cells and new targets for therapy. Other GBM animal models include established glioma cell lines (human and rodent) implanted intracranially into immunodeficient or immunocompetent animals, and genetically engineered mice that spontaneously develop brain tumors or are induced with viral vectors. 10 GENE DELIVERY VEHICLES FOR GLIOBLASTOMAMost gene therapies for GBM use biologic vectors such as viruses or cells. Replicationdefective or non-repli...

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Section: Stem Cells As Oncolytic Virus Carriersmentioning

confidence: 98%

Section: Stem Cells As Oncolytic Virus Carriersmentioning

confidence: 99%

Current Status of Gene Therapy for Brain Tumors∗

Ning

Rabkin

2015

Translating Gene Therapy to the Clinic

View full text Add to dashboard Cite

show abstract

“…Investigators have demonstrated the in vivo migratory capacity of stem cells toward primary GBM tumors as well as invasive tumor cells that intermingle with normal brain tissue (19)(20)(21)(22)(23)(24)(25)(26)(27)(28). Various stem cells such as embryonic stem cells, mesenchymal stem cells, neural stem cells, induced pluripotent stem cells (iPSCs), and neural stem cells derived from iPSCs have been shown to migrate to intracranially established GBMs when implanted loco-regionally within the brain, and their ability to secrete anti-GBM therapies after genetic modification has been investigated (29).…”

Section: Controllable Drug Delivery Using Stem Cells In Conjunction Wmentioning

confidence: 99%

Maximizing Local Access to Therapeutic Deliveries in Glioblastoma. Part IV: Image- Guided, Remote-Controlled Opening of the Blood–Brain Barrier for Systemic Brain Tumor Therapy

et al. 2017

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Disease in the central nervous system (CNS) is a challenge to treat with systemic therapies due to the presence of the blood-brain barrier (BBB), which excludes common and novel therapeutics. For example, glioblastoma (GBM) is the most common and aggressive primary brain tumor, with an extremely poor prognosis due to infiltrating tumor cells in areas of normal brain. A primary On-Demand Opening of the BBB 396 challenge of treating this devastating disease is the exclusion of systemic therapies from the CNS. While efforts are being made to develop strategies for designing drugs that can pass through the BBB, there are also efforts to use novel engineering techniques to safely allow any systemic therapy into the CNS and areas of disease. In this chapter, we focus on using high-intensity focused ultrasound (HIFU) to circumvent the BBB.

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“…Mesenchymal stromal cells loaded with Ad-D24RGD have been able to migrate to and infect intracerebral gliomas, whereas Ad-D24RGD alone was unable to do so. 87 …”

Section: Gene Therapy For Brain Tumorsmentioning

confidence: 99%

Current standing and frontiers of gene therapy for meningiomas

Ramos

Flores-Rodríguez

Martínez-Gutiérrez

et al. 2013

FOC

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Meningiomas are among the most common intracranial tumors. The treatment of choice for these lesions is complete resection, but in 50% of cases it is not achieved due to tumor location and/or surgical morbidities. Moreover, benign meningiomas have high recurrence rates of up to 32% in long-term follow-up. Molecular analyses have begun to uncover the genetics behind meningiomas, giving rise to potential genetics-based treatments, including gene therapy. The authors performed a literature review on the most relevant genes associated with meningiomas and both current and potential gene therapy strategies to treat these tumors. Wild-type NF2 gene insertion, oncolytic viruses, and transfer of silencing RNA have all shown promising results both in vitro and in mice. These strategies have decreased meningioma cell growth, proliferation, and angiogenesis. However, no clinical trial has been done to date. Future research and trials in gene insertion, selective inhibition of oncogenes, and the use of oncolytic viruses, among other potential treatment approaches, may shape the future of meningioma management.

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Human Bone Marrow–Derived Mesenchymal Stem Cells for Intravascular Delivery of Oncolytic Adenovirus Δ24-RGD to Human Gliomas

Cited by 221 publications

References 37 publications

Current Status of Gene Therapy for Brain Tumors∗

Current Status of Gene Therapy for Brain Tumors∗

Maximizing Local Access to Therapeutic Deliveries in Glioblastoma. Part IV: Image- Guided, Remote-Controlled Opening of the Blood–Brain Barrier for Systemic Brain Tumor Therapy

Current standing and frontiers of gene therapy for meningiomas

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