Gene therapy for high grade gliomas.
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.
Alavi
J B
JB
Hematology-Oncology Division, Department of Medicine, University of Pennsylvania, 3400 Spruce St., Philadelphia 19104, USA. jalavi@mail.med.upenn.edu
Eck
S L
SL
D000256:Adenoviridae / Q000235:genetics; D016543:Central Nervous System Neoplasms / Q000235:genetics / Q000628:therapy; D002986:Clinical Trials as Topic; D015774:Ganciclovir / Q000378:metabolism / Q000494:pharmacology; D015316:Genetic Therapy / Q000379:methods* / Q000639:trends; D005822:Genetic Vectors / Q000235:genetics; D005910:Glioma / Q000235:genetics* / Q000628:therapy*; D006801:Humans; D012190:Retroviridae / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D016159:Tumor Suppressor Protein p53; D013937:Thymidine Kinase; D015774:Ganciclovir