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Gene therapy for high grade gliomas
1Hematology-Oncology Division, Department of Medicine, University of Pennsylvania, 3400 Spruce St., Philadelphia 19104, USA. jalavi@mail.med.upenn.edu
Abstract:
High grade gliomas in adults are devastating diseases, with very poor survival despite their lack of distant metastases. Local treatments, such as surgical resection and stereotactic radiosurgery, have been most successful, whereas systemic therapy (for example, chemotherapy and immunotherapy) have been rather disappointing. Several gene therapy systems have been successful in controlling or eradicating these tumours in animal models and are now being tested as a logical addition to current clinical management. This review describes the gene therapy clinical protocols that have been completed or that are ongoing for human gliomas. These include the prodrug activating system, herpes simplex thymidine kinase (HSVtk)/ganciclovir (GCV), utilising either retrovirus vector producer cells or adenovirus vectors; adenovirus mediated p53 gene transfer; adenovirus mediated IFN-beta gene transfer and oncolytic herpes virus and adenovirus vectors. To date, all of the clinical studies have used direct injection of the vector into the glioma. The Phase I clinical studies have demonstrated low to moderate toxicity and variable levels of gene transfer and in some cases anti-tumour effect. Future directions will rely upon improvements in gene delivery as well as gene therapies and combinations of gene therapy with other treatment modalities.
Insights
Gene therapy shows promise for high-grade gliomas, offering a new approach beyond traditional treatments. Clinical trials demonstrate manageable toxicity and potential anti-tumor effects, paving the way for future advancements.
Area of Science:
- Neuro-oncology
- Molecular therapy
- Clinical gene transfer
Background:
- High-grade gliomas (HGGs) are aggressive brain tumors with poor prognoses.
- Current systemic therapies like chemotherapy and immunotherapy have limited efficacy in HGGs.
- Local treatments offer better outcomes but are insufficient for complete eradication.
Purpose of the Study:
- To review completed and ongoing gene therapy clinical protocols for adult gliomas.
- To summarize the methodologies and outcomes of these gene therapy trials.
- To identify future directions for gene therapy in glioma treatment.
Main Methods:
- Direct intratumoral injection of viral vectors into gliomas.
- Utilized vectors include retroviruses, adenoviruses, and oncolytic viruses.
- Gene therapy strategies encompass prodrug activation (HSVtk/ganciclovir), p53, and IFN-beta gene transfer.
Main Results:
- Phase I clinical studies indicate low to moderate toxicity.
- Variable levels of gene transfer efficiency were observed.
- Some studies reported evidence of anti-tumor effects.
Conclusions:
- Gene therapy represents a promising addition to HGG management.
- Improvements in gene delivery systems are crucial for enhanced efficacy.
- Combination of gene therapy with other modalities holds significant future potential.