1. Efficacy of adenovirally expressed soluble TRAIL in human glioma organotypic slice culture and glioma xenografts
- Author
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Jingda Xu, Sujit S. Prabhu, Vinay K. Puduvalli, Frederick F. Lang, Xiao-Ming Xie, Gregory N. Fuller, Kenneth Aldape, Yuexin Liu, and Deepa Sampath
- Subjects
Cancer Research ,Pathology ,medicine.medical_specialty ,Genetic Vectors ,Immunology ,Mice, Nude ,Biology ,medicine.disease_cause ,Adenoviridae ,Green fluorescent protein ,TNF-Related Apoptosis-Inducing Ligand ,Mice ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Cell Line, Tumor ,Glioma ,Bystander effect ,medicine ,Animals ,Frozen Sections ,Humans ,Cell Proliferation ,030304 developmental biology ,0303 health sciences ,organotypic slice cultures ,Brain Neoplasms ,Cell growth ,soluble TRAIL ,apoptosis ,adenovirus ,Genetic Therapy ,Cell Biology ,medicine.disease ,3. Good health ,Apoptosis ,030220 oncology & carcinogenesis ,Toxicity ,Cancer research ,Original Article ,Female ,Tumor necrosis factor alpha ,Neoplasm Transplantation - Abstract
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in malignant cells, including gliomas, and is currently in anticancer clinical trials. However, the full-length and tagged forms of TRAIL, unlike the untagged ligand (soluble TRAIL (sTRAIL)), exhibits toxicity against normal cells. Here, we report the generation and testing of an adenovirus (AdsTRAIL) that expresses untagged sTRAIL in an intracranial xenograft model and a human glioma organotypic slice culture model. AdsTRAIL efficiently induced apoptosis in glioma cell lines, including those resistant to sTRAIL, but not in normal human astrocytes (NHAs). It inhibited anchorage-independent glioma growth and exerted a bystander effect in transwell assays. Intratumoral injections of AdsTRAIL in a rodent intracranial glioma model resulted in reduced tumor growth and improved survival compared with Ad-enhanced green fluorescent protein (EGFP)- or vehicle-treated controls without toxicity. Human glioma organotypic slices treated with AdsTRAIL demonstrated apoptosis induction and caspase activation.
- Published
- 2011
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