Abstract
Purpose: Glioblastoma multiforme is a deadly primary brain cancer. Because the tumor kills due to recurrences, we tested the hypothesis that a new treatment would lead to immunological memory in a rat model of recurrent glioblastoma multiforme. Experimental Design: Wedeveloped a combined treatment using an adenovirus (Ad) expressing fms-like tyrosine kinase-3 ligand (Flt3L),which induces the infiltration of immune cells into the tumor microenvironment, and an Ad expressing herpes simplex virus-1-thymidine kinase (TK), which kills proliferating tumor cells in the presence of ganciclovir. Results: This treatment induced immunologicalmemory that led to rejection of a second glioblastoma multiforme implanted in the contralateral hemisphere and of an extracranial glioblastomamultiforme implanted intradermally. Rechallenged long-termsurvivors exhibited anti-glioblastoma multiforme-specific T cells and displayed specific delayedtype hypersensitivity. Using depleting antibodies,we showed that rejection of the second tumor was dependent on CD8+ T cells. Circulating anti