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Combined HSV-TK/IL-2 gene therapy in patients with recurrent glioblastoma multiforme: biological and clinical results

Cancer Gene Therapy volume 12, pages 835–848 (2005)Cite this article

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.

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Acknowledgements

This work was supported by grants from MIUR no. 2002062741 and FIRB no. RBNE0127YS-006.

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Author notes

  1. Federico Colombo and Luisa Barzon: The first two authors contributed equally to this work.

Authors and Affiliations

  1. Division of Neurosurgery, San Bortolo Hospital, Vicenza, Italy

    Federico Colombo & Mariano Zanusso

  2. Department of Histology, Microbiology and Medical Biotechnologies, University of Padova, Padova, Italy

    Luisa Barzon, Elisa Franchin, Monia Pacenti & Giorgio Palù

  3. Neuroradiology Service, San Bortolo Hospital, Vicenza, Italy

    Vittore Pinna

  4. Pathology Service, San Bortolo Hospital, Vicenza, Italy

    Daniela Danieli

Authors
  1. Federico Colombo
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  2. Luisa Barzon
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Correspondence to Giorgio Palù.

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Colombo, F., Barzon, L., Franchin, E. et al. Combined HSV-TK/IL-2 gene therapy in patients with recurrent glioblastoma multiforme: biological and clinical results. Cancer Gene Ther 12, 835–848 (2005). https://doi.org/10.1038/sj.cgt.7700851

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