Gene Therapy
The Maxine Dunitz Neurosurgical Institute is also aggressively pursuing new gene-therapy strategies for intracranial lesions, modifying brain tumors to make them more vulnerable to attack either by the immune system or by chemotherapeutic drugs. Our scientists are focused specifically on genetic research as it relates to immunotherapy, investigating potential viruses to shuttle therapeutic genes to treat brain tumors.
We have assessed the efficacy and safety of a replication conditional HSV mutant in vitro and in vivo. This virus, named DM33, contains deletions in the gamma 34.5 gene and the LAT gene. It is safe and effective in the treatment of experimental brain tumors, and we are developing its use for patients with glioblastoma. We are studying a virus based on the DM33 virus with constitutive expression of the human interferon gamma gene, which may hold promise for immunologic gene therapy. We are also collaborating on constructing a tetracycline responsive herpes vector containing the kringle 5 antiangiogenesis gene. These projects will be performed to develop an effective virus based on cytolytic and immunologic strategies to be translated in two years for clinical use. Adenoviral interferon gamma and tumor necrosis factor alpha have been delivered intratumorally in intracranial glioma models. We hope to determine local cytokine effects in engendering local immunologic recognition. This strategy will be used to augment antigen presentation performed peripherally. Three mechanisms of tumor killing via intra-arterial gene delivery will be exploited: a cytolytic mechanism with herpes simplex mutants, an immunologic mechanism, and antiangiogenesis.
Recent Publications
Ehtesham M, Kabos P, Kabosova A, Neuman T, Black KL, Yu JS. The use of interleukin 12 secreting neural stem cells for the treatment of intracranial glioma. Cancer Research 62:5657-5663, 2002. Cover article.
Kabos, Peter, Ehtesham, M., Kabosova, A., Black, K.L., and Yu, J.S: Neural progenitor cells from whole adult bone marrow. Experimental Neurology 178(2): 288-293, 2002. Cover article.
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