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Abstract

Grant Number:	1R41CA103269-01
PI Name:	WHITT, MICHAEL A.
PI Email:	mwhitt@gtxinc.com
PI Title:	DIRECTOR AND PROFESSOR
Project Title:	Developing VSV cytolytics against High-Grade CNS gliomas

Abstract: DESCRIPTION (provided by applicant): Despite continued improvements in diagnosis, surgical techniques, and radiation protocols, the available treatments for high-grade malignant glioma are grossly inadequate. The median survival time for most patients with high-grade gliomas is on the order of months. Metastatic tumors with a tropism for the CNS such as lung and breast pose an even greater problem. These tumors are five times more common than primary CNS tumors and have an equally devastating prognosis. Because surgery is the only therapy currently available that provides some benefit for these patients, the development of a potent adjuvant to surgery could indeed tip the balance towards a better outcome. Such an adjuvant would need to target micropopulations of ceils that are missed by gross surgical resection. One approach that has given promising results in preclinical animal studies and that has shown some success in clinical trials is the use of oncolytic viruses for treatment of brain tumors. A recent addition to the list of viruses that are being considered for oncolytic therapy is Vesicular stomatitis virus (VSV). Based on encouraging preliminary data, this proposal is designed to evaluate the application of recombinant VSVs (rVSVs) for the treatment of high-grade gliomas. The goal of this phase I STTR application is to obtain proof-of-principal data on the utility of VSV-based Vectors to reduce tumor-burden in a rodent model for gliomas. Aim I will evaluate the efficacy and specificity of tumor targeting by VSV in a novel, ex vivo organotypic brain slice culture system developed by scientists at the University of Tennessee Health Science Center. Our working hypothesis is that VSV will preferentially infect and kill tumor cells over cells derived from normal tissues in the organotypic culture system due to defects in the anti-viral responses of the tumor cells. Aim II will examine the efficacy and safety of VSV anti-rumor cytolytics in an in vivo intracranial glioma model. Together these studies will provide critical proof-of-concept data, which will lead to more detailed studies using glioma-specific targeting vectors.

Thesaurus Terms:
Vesiculovirus, carcinogenesis inhibitor, cytolysis, glioma, immunity, neoplasm /cancer remission /regression, neoplasm /cancer therapy, technology /technique development, transfection /expression vector, virus infection mechanism
apoptosis, disease /disorder model, interferon beta, virus replication
biotechnology, laboratory mouse, laboratory rat, sectioning

Institution:	GTX, INC.
	VAN VLEET BLDG, 3RD FL
	MEMPHIS, TN 38163
Fiscal Year:	2003
Department:
Project Start:	30-SEP-2003
Project End:	31-AUG-2004
ICD:	NATIONAL CANCER INSTITUTE
IRG:	ZRG1

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