Margarita Gutova,
Assistant Research Professor,
City of Hope National Cancer Center
Margarita Gutova, M.D. is Assistant Research Professor and leading scientist investigating the novel utility of a well established human neural stem cell (NSC) line for tumor-selective delivery of therapeutic gene products in preclinical models of brain tumors. By circumventing the blood brain barrier, NSCs can overcome a major obstacle to pharmacologic treatment of tumors of central nervous system. NSCs are modified to secrete an enzyme that activates the prodrug to the active anticancer drug. This innovative NSC - mediated enzyme/prodrug approach will localize drug concentrations specifically to brain tumor foci and significantly improve clinical outcome, while minimizing the devastating side effects associated with toxicity to normal tissues. These studies paved the way towards the first-in-human clinical trial of these NSCs to assess the safety of NSC-mediated CD/5-FC enzyme/prodrug therapy in patients with recurrent high-grade glioma.
Intranasal Delivery of Therapeutic NSCs to Target Intracerebral Glioma: Enzyme/Prodrug CE/CPT-11 Therapy
Friday, 6 September 2013 at 17:00
Add to Calendar ▼2013-09-06 17:00:002013-09-06 18:00:00Europe/LondonIntranasal Delivery of Therapeutic NSCs to Target Intracerebral Glioma: Enzyme/Prodrug CE/CPT-11 TherapyStem Cells and Cell Therapy Summit in London, UKLondon, UKSELECTBIOenquiries@selectbiosciences.com
Despite aggressive multimodal therapy and advances in imaging, surgical and radiation techniques, high-grade gliomas remain incurable, with survival often measured in months. Treatment failure is largely attributable to the diffuse and invasive nature of glioma cells, ineffective delivery of chemotherapeutic agents across the blood-brain barrier (BBB), and associated dose-limiting systemic toxicities. Neural stem cells (NSCs) display inherent tumor-tropic properties that can be exploited for targeted delivery of anti-cancer agents to invasive and metastatic tumors, and may offer an unprecedented advantage over conventional therapeutic approaches. NSCs can overcome the major obstacles limiting the efficacy of current treatments by their ability to cross the BBB, target therapeutic agents to primary and invasive tumor foci throughout the brain, and minimize toxicity to normal tissues. Used as a delivery vehicle, NSCs have been engineered to express a variety of anti-cancer agents, demonstrating >70% therapeutic efficacy in pre-clinical models of glioma, medulloblastoma, melanoma brain metastases and disseminated neuroblastoma. Cell based therapies for neurodegenerative diseases depend on efficient delivery of the therapeutic cells to the areas of damage. Administration of NSCs intracranially may cause damage of normal tissues and demonstrate poor engraftment into the brain. Alternatively, when stem cells are injected intravenously immunological reaction and other systemic complications may occur. Here we demonstrate, for the first time, tumor-specific NSC tropism of therapeutic human neural stem cells (HB1.F3.CDs) to human glioma xenografts in mouse models. In this study, severely immunodeficient Esl1 were implanted intracranially with U251.eGFP.ffluc glioma cells. After 15 days, NSCs were administered intranasally and biodistribution of the stem cells was determined via MR and histological imaging.
Add to Calendar ▼2013-09-05 00:00:002013-09-06 00:00:00Europe/LondonStem Cells and Cell Therapy SummitStem Cells and Cell Therapy Summit in London, UKLondon, UKSELECTBIOenquiries@selectbiosciences.com
Add to Calendar ▼2013-09-06 17:00:002013-09-06 18:00:00Europe/LondonIntranasal Delivery of Therapeutic NSCs to Target Intracerebral Glioma: Enzyme/Prodrug CE/CPT-11 TherapyStem Cells and Cell Therapy Summit in London, UKLondon, UKSELECTBIOenquiries@selectbiosciences.com
