Targeted Adenoviral Gene Therapy for Malignant Glioma

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DESCRIPTION (provided by applicant): High grade gliomas represent the most common primary malignant tumor of the adult central nervous system. Unfortunately, the median survival after surgical intervention alone is only six months and the addition of radiotherapy can extend this time to only nine months. Consequently, efforts aimed at developing new therapies have focused on new treatment strategies that specifically target tumor cells and spare normal cells. One such modality, gene therapy, has shown promise in the spectrum of agents utilized against brain tumors. The success of gene therapy depends on efficient gene delivery into target cells. Viral vectors, in the form of adenoviruses, have provided one potential means for the delivery of gene therapy. Several studies, however, have demonstrated a relative resistance of brain tumors to adenoviral vectors, a finding that was subsequently attributed to the quantitative deficiency of the primary adenoviral receptor, the Coxsackie Adenovirus Receptor (CAR), on tumor cells. The main purpose of this project is to develop re-targeted adenoviral vectors with the capacity to enhance immune based cancer therapies. The focus of the re-targeting has been the expression of alpha-v-beta3 and alpha-v-beta5 on many solid organ tumors. This project aims to develop second generation adenoviruses with altered tropism for alpha-v-beta3 and alpha-v-beta5 integrins in order to achieve cell-specific targeting of immune-modulatory genes. The principal investigator, Dr. Maciej S. Lesniak, has recently completed his residency in neurological surgery and is currently as Assistant Professor of Neurosurgery at the Johns Hopkins Hospital. Dr. Lesniak immediate goals are to establish a solid research background that will allow him to become an independent investigator. By undertaking this project and furthering his scientific and biomedical research education, Dr. Lesniak hopes to one day translate this research to the clinical setting and the treatment of patients with malignant brain tumors.