1. ¹Division of Neurosurgery, San Bortolo Hospital, Vicenza, Italy
2. ²Department of Histology, Microbiology and Medical Biotechnologies, University of Padova, Padova, Italy
3. ³Neuroradiology Service, San Bortolo Hospital, Vicenza, Italy
4. ⁴Pathology Service, San Bortolo Hospital, Vicenza, Italy

Correspondence: Professor Giorgio Palù, MD, Department of Histology, Microbiology and Medical Biotechnologies, University of Padova, via A Gabelli 63, I-35121 Padova, Italy. E-mail giorgio.palu@unipd.it

^aThe first two authors contributed equally to this work.

Received 25 October 2004; Published online 13 May 2005.

Abstract

Following our pilot clinical study of combined IL-2/HSV-TK gene therapy for recurrent glioblastoma multiforme (GBM), we extended the protocol to a larger population of patients and evaluated safety, feasibility, and biological activity of treatment. A total of 12 patients received intratumor injection of retroviral vector-producing cells (RVPCs), followed by intravenous ganciclovir (GCV). Treatment was well tolerated with only minor adverse events. Transduction of tumor cells was demonstrated in tumor biopsies. A marked and persistent increase of intratumor and plasma Th1 cytokine levels was demonstrated after RVPC injection. At magnetic resonance imaging evaluation, two patients had a partial response (including a patient showing disappearance of a distant noninjected tumor mass), four had a minor response, four had stable disease, and two had progressive disease. The 6- and 12-month progression-free survival rates were 47 and 14%, respectively. The 6- and 12-month overall survival rates were 58 and 25%, respectively. In conclusion, the results of our clinical protocol of gene therapy for recurrent GBM, based on combined delivery of a suicide and a cytokine gene, demonstrate that intratumor injection of RVPCs was safe, provided effective transduction of the therapeutic genes to target tumor cells, and activated a systemic cytokine cascade, with tumor responses in 50% of cases.