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Gene Transfer into Brain Parenchyma Elicits Antitumor Effects¹

Departments of Neurology [H. M. F-S., A. I. K., L-J. Z.], Anesthesia and Pain Management [G. M. S.], and Center For Immunology [J. F.], The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75235

Gene therapy strategies for cancer currently aim at targeting gene delivery to the malignant cell. In a mouse model of intracerebral Lewis lung carcinoma (3LL), adenoviral vectors transduce not only 3LL cells but also brain parenchymal cells including endothelial cells, neurons, microglia, and astrocytes in vivo. Furthermore, transgene expression persists longer in brain than in tumor. Transfer of IFN- into brain parenchymal cells rather than tumor is both necessary and sufficient to generate antitumor therapeutic benefits. Therefore, parenchymal cells represent an effective and necessary target for delivery of genes that render the brain uninhabitable by the tumor.