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Local inflammation and devascularization — in vivo mechanisms of the “bystander effect” in VPC-mediated HSV-Tk/GCV gene therapy for human malignant glioma

Cancer Gene Therapy volume 8, pages 843–851 (2001)Cite this article

Abstract

Somatic gene therapy with the herpes simplex virus type I thymidine kinase gene/ganciclovir (HSV-Tk/GCV) system and murine retroviral vector producer cells (VPCs) was introduced as a new adjuvant treatment modality to treat tumor bulk and to prevent tumor recurrence in patients harboring malignant glioma. The single-center experience after treatment of 27 patients undergoing tumor resection followed by intracerebral VPC injection for HSV-Tk suicide gene therapy will be presented focused on findings of systematic and close MRI follow-up and a few histological specimens. The data indicate that hemorrhagic necrosis due to endothelial cell transfection mediated vessel necrosis and that local inflammatory immune response occurs frequently after gene therapy. These phenomena seem to be specific because none of the patients of a control group showed any similar features. The prognosis (time to progression, survival) of the patients with “bystander effects” after gene therapy was better, but compared to those patients without bystander effects, they were also privileged by a favorable constellation of prognostic factors. Therefore, the appearance of these neuroradiologic features cannot serve as an indicator for treatment effectiveness and outcome. Cancer Gene Therapy (2001) 8, 843–851

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Acknowledgements

We thank the staff of all cooperating institutions that were involved in the investigation of the specimens and gathering the data for our study. Especially, the assistance of Susanne Beyer and Michael Krämer from the Neurosurgical Institute of Electronic Data Processing in preparing the raw data and presenting the imaging is gratefully acknowledged.

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Authors and Affiliations

  1. Department of Neurosurgery, Heinrich-Heine-University, Düsseldorf, Germany

    Frank W Floeth, Wolfgang J Bock & Friedrich Weber

  2. Oncology Clinical Research, Novartis Pharma, Basel, Switzerland

    Nick Shand

  3. Department of Oncologic Chemistry, Heinrich-Heine-University, Düsseldorf, Germany

    Hans Bojar & Hans B Prisack

  4. Department of Neuropathology, Heinrich-Heine-University, Düsseldorf, Germany

    Jörg Felsberg & Eva Neuen-Jacob

  5. Department of Diagnostic Radiology, Heinrich-Heine-University, Düsseldorf, Germany

    Albrecht Aulich

  6. Novartis Pharma AG, Nürnberg, Germany

    Klaus J Burger

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  1. Frank W Floeth
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  2. Nick Shand
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  3. Hans Bojar
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  9. Wolfgang J Bock
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  10. Friedrich Weber
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Correspondence to Frank W Floeth.

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Floeth, F., Shand, N., Bojar, H. et al. Local inflammation and devascularization — in vivo mechanisms of the “bystander effect” in VPC-mediated HSV-Tk/GCV gene therapy for human malignant glioma. Cancer Gene Ther 8, 843–851 (2001). https://doi.org/10.1038/sj.cgt.7700382

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