Chapter

Gene Therapy of Glioblastoma Multiforme - Clinical Experience on the Use of Adenoviral Vectors

In book: Brain Tumors - Current and Emerging Therapeutic Strategies
Source: InTech
0 Bookmarks
 · 
123 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Gliomas are among the most lethal malignancies, and constitute more than 70% of all brain tumors. Standard therapy includes surgical resection followed by adjuvant radiotherapy and/or chemotherapy. Malignant gliomas are considered to be non-curable, and the overall prognosis of treatment success is poor with a mean survival of 14.6 months after diagnosis and a 5-year survival rate of 9.8%. The diffusely infiltrating property of the tumors makes total surgical excision often impossible, leading to eventual tumor recurrence. The maximum radiation dose that can be administered to the brain is limited to approximately 60 Gy, which is usually not sufficient to completely eradicate the tumor given that some brain tumors are resistant to radiotherapy. The limitations and short-comings of the available treatment options have provided the impetus to test novel therapy modalities to improve quality of life and increase survival of patients with gliomas.
    Current opinion in molecular therapeutics 10/2009; 11(5):485-92. · 3.42 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A study was made of the consequences of the introduction, by superinfection or mutation, of a marked type of Rous sarcoma virus (RSV) into chicken embryonic cells already infected with RSV. Characters controlling cell morphology (Temin, 1960) were used as markers.After superinfection, cells can release virus of the original type only, of the superinfecting type only, or of both the original and superinfecting types. Over ten generations after superinfection, single cells can release two types of virus. Cells which release both viruses can have the morphology of either type; the virus that controls cell type can be either the original or the superinfecting virus.It was found that the proportion of mutant virus and the proportion of mutant cells in clonal populations of Rous sarcoma cells was similar.
    Virology 03/1961; · 3.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The retrovirus-mediated transfer of the herpes simplex virus-thymidine kinase (HSV-tk) gene into tumor cells renders them sensitive to the cytocidal effect of the antiviral drug ganciclovir. This method has shown promising results as a treatment for experimental brain tumors. These experiments indicate that a major mechanism for the effectiveness of HSV-tk retroviral gene therapy may be the bystander tumoricidal effect. The bystander effect was hypothesized to explain tumor eradication, given that the efficacy of in vivo gene transfer to tumor cells was less than 100%. We demonstrate, in this report, that the bystander tumoricidal effect is a major contributor to the tumoricidal effect of ganciclovir in cell culture experiments using the mouse K1735 C19 cerebral melanoma line, thereby expanding the observation of the bystander phenomenon to a broader range of tumor types. The bystander effect was studied in vitro by coculturing wild-type C19 melanoma cells with HSV-tk-expressing C19 (C19-STK) cells. A maximal tumoricidal effect was seen when only 1 in 10 tumor cells expressed the HSV-tk gene. This suggests that in effect, 1 tumor cell with the HSV-tk gene, when given ganciclovir, will destroy 10 neighboring or bystander cells. The destruction of bystander cells does not appear to be mediated by a soluble factor(s) released into the media but, rather, requires close cell proximity or cell contact. In addition, HSV-tk-expressing C19 cells can exert an antitumoral effect not only on wild-type C19 cells but also on cells from a variety of different tumor cell lines, including a human glioblastoma multiforme cell line, indicating that the bystander effect is not a cell line-specific phenomenon. Finally, we observed that the bystander tumoricidal effect could be harnessed directly without using retrovirus-producing cells to increase survival in the mouse C19 brain tumor model. The potential implications of our findings in treating human brain tumors are discussed.
    Neurosurgery 01/1995; 35(6):1094-102; discussion 1102-3. · 2.53 Impact Factor

Full-text

View
2 Downloads
Available from