Current status of gene therapy for brain tumors

Abstract

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 replication-competent 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.

New Treatment Modalities for Brain Tumors in Dogs and Cats

“…[23][24][25] Reviews of boron neutron capture therapy, brachytherapy, high-intensity focused ultrasound (HiFU), gene therapy, laser interstitial thermal therapy, proton beam radiotherapy, oncolytic viruses, and pulsed electric fields are available elsewhere. 7,[26][27][28][29][30][31][32][33][34] These therapeutic approaches are not mutually exclusive. For example, because many molecularly targeted chemotherapeutics, gene-bearing vectors, and boron delivery agents are high-molecular-weight structures that cannot penetrate the BBB when administered systemically, they require delivery by a method that bypasses or disrupts the BBB, such as CED or HiFU.…”

Identification of Postoperative Margins of Glioblastoma Multiforme Using Gold Nanoparticles Conjugated to Epidermal Growth Factor Antibodies

“…Although the high levels of EGFR in some forms of GBM also make it an accurate and desirable therapeutic target, current therapies targeting EGFR, including tyrosine kinase inhibitors and RNA interference, have proved to be ineffective [7,8,34]. Therefore, attention is being addressed to other means: the delivery of novel antitumor agents across the blood-brain barrier, gene therapy, and brain tumor vaccines [35][36][37]. One study found that the use of metallic nanoparticles conjugated to anti-EGFR antibody combined with cisplatin could eradicate tumor cells when subjected to radiation in vitro [38].…”

Current standing and frontiers of gene therapy for meningiomas

“…61 An advantage to this method is that viruses can be dispensed intravascularly, thus evading antiviral immunity and being able to reach the tumor from a distance. 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.…”