Gene Therapy and Targeted Toxins for Glioma
Maria G. Castro,Marianela Candolfi,Kurt M. Kroeger,Gwendalyn D. King,James F. Curtin,Kader Yagiz,Yohei Mineharu,Hikmat Assi,Mia Wibowo,A.K.M. Ghulam Muhammad,David Foulad,Mariana Puntel,Pedro R. Lowenstein +12 more
TLDR
This review will examine the available preclinical models for glioma including xenographs, syngeneic and genetic models to determine which strategies will provide rapid tumor regression and long-term protection from recurrence.Abstract:
The most common primary brain tumor in adults is glioblastoma. These tumors are highly invasive and aggressive with a mean survival time of nine to twelve months from diagnosis to death. Current treatment modalities are unable to significantly prolong survival in patients diagnosed with glioblastoma. As such, glioma is an attractive target for developing novel therapeutic approaches utilizing gene therapy. This review will examine the available preclinical models for glioma including xenographs, syngeneic and genetic models. Several promising therapeutic targets are currently being pursued in pre-clinical investigations. These targets will be reviewed by mechanism of action, i.e., conditional cytotoxic, targeted toxins, oncolytic viruses, tumor suppressors/oncogenes, and immune stimulatory approaches. Preclinical gene therapy paradigms aim to determine which strategies will provide rapid tumor regression and long-term protection from recurrence. While a wide range of potential targets are being investigated preclinically, only the most efficacious are further transitioned into clinical trial paradigms. Clinical trials reported to date are summarized including results from conditionally cytotoxic, targeted toxins, oncolytic viruses and oncogene targeting approaches. Clinical trial results have not been as robust as preclinical models predicted, this could be due to the limitations of the GBM models employed. Once this is addressed, and we develop effective gene therapies in models that better replicate the clinical scenario, gene therapy will provide a powerful approach to treat and manage brain tumors.read more
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Intracranial glioblastoma models in preclinical neuro-oncology: neuropathological characterization and tumor progression
Marianela Candolfi,Marianela Candolfi,James F. Curtin,James F. Curtin,W. Stephen Nichols,Akm Ghulam Muhammad,Gwendalyn D. King,Gwendalyn D. King,G. Elizabeth Pluhar,Elizabeth A. McNiel,John R. Ohlfest,Andrew Freese,Peter F Moore,Jonathan Lerner,Jonathan Lerner,Pedro R. Lowenstein,Pedro R. Lowenstein,Maria G. Castro,Maria G. Castro +18 more
TL;DR: The data indicate that murine models of GBM appear to recapitulate several of the human GBM histopathological features and, considering their reproducibility and availability, they constitute a valuable in vivo system for preclinical studies.
Journal ArticleDOI
Glioblastoma multiforme: State of the art and future therapeutics
TL;DR: Treatment of Glioblastoma multiforme remains extremely challenging, and continued research and development of targeted therapies, based on a detailed understanding of molecular pathogenesis can reasonably be expected to yield improved outcomes for patients with GBM.
Journal ArticleDOI
Glioblastoma multiforme – an overview
TL;DR: The biology of glioblastoma multiforme has recently been widely investigated, but the studies summarizing the knowledge of its development and treatment are still not sufficient in terms of comprehensive brain tumor analysis.
Journal ArticleDOI
Progress in gene therapy for neurological disorders
Michele Simonato,Jean Bennett,Nicholas M. Boulis,Maria G. Castro,David J. Fink,William F. Goins,Steven J. Gray,Pedro R. Lowenstein,Luk H. Vandenberghe,Thomas J. Wilson,John H. Wolfe,Joseph C. Glorioso +11 more
TL;DR: The promising gene therapy strategies that have the potential to treat patients with neurological diseases are described and prospects for future development of gene therapy are discussed.
Journal ArticleDOI
Expression of MHC I and NK ligands on human CD133 + glioma cells: possible targets of immunotherapy
Anhua Wu,Anhua Wu,Stephen M. Wiesner,Jing Xiao,Katya Ericson,Wei Chen,Walter A. Hall,Walter C. Low,John R. Ohlfest +8 more
TL;DR: It is concluded that CD 133-posistive and CD133-negative glioma cells may be similarly resistant to immune surveillance, but that INF-γ may partially restore their immunogenicity and potentiate their lysis by NK cells.
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