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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08NS046430-03
Application #
7236585
Study Section
NST-2 Subcommittee (NST)
Program Officer
Fountain, Jane W
Project Start
2005-07-15
Project End
2010-04-30
Budget Start
2007-05-01
Budget End
2008-04-30
Support Year
3
Fiscal Year
2007
Total Cost
$165,078
Indirect Cost
Name
University of Chicago
Department
Surgery
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
Dey, Mahua; Ulasov, Ilya V; Tyler, Matthew A et al. (2011) Cancer stem cells: the final frontier for glioma virotherapy. Stem Cell Rev 7:119-29
Rozhkova, E A; Ulasov, I V; Kim, D-H et al. (2011) MULTIFUNCTIONAL NANO-BIO MATERIALS WITHIN CELLULAR MACHINERY. Int J Nanosci 10:899
Ahmed, Atique U; Rolle, Cleo E; Tyler, Matthew A et al. (2010) Bone marrow mesenchymal stem cells loaded with an oncolytic adenovirus suppress the anti-adenoviral immune response in the cotton rat model. Mol Ther 18:1846-56
Balyasnikova, Irina V; Franco-Gou, Rosa; Mathis, J Michael et al. (2010) Genetic modification of mesenchymal stem cells to express a single-chain antibody against EGFRvIII on the cell surface. J Tissue Eng Regen Med 4:247-58
Sengupta, Sadhak; Nandi, Suvobroto; Hindi, Enal S et al. (2010) Short hairpin RNA-mediated fibronectin knockdown delays tumor growth in a mouse glioma model. Neoplasia 12:837-47
Balyasnikova, Irina V; Ferguson, Sherise D; Sengupta, Sadhak et al. (2010) Mesenchymal stem cells modified with a single-chain antibody against EGFRvIII successfully inhibit the growth of human xenograft malignant glioma. PLoS One 5:e9750
Dey, Mahua; Ulasov, Ilya V; Lesniak, Maciej S (2010) Virotherapy against malignant glioma stem cells. Cancer Lett 289:1-10
Kim, Dong-Hyun; Rozhkova, Elena A; Ulasov, Ilya V et al. (2010) Biofunctionalized magnetic-vortex microdiscs for targeted cancer-cell destruction. Nat Mater 9:165-71
Nandi, Suvobroto; Lesniak, Maciej S (2009) Adenoviral virotherapy for malignant brain tumors. Expert Opin Biol Ther 9:737-47
Kranzler, Justin; Tyler, Matthew A; Sonabend, Adam M et al. (2009) Stem cells as delivery vehicles for oncolytic adenoviral virotherapy. Curr Gene Ther 9:389-95

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