Local inflammation and devascularization — in vivo mechanisms of the “bystander effect” in VPC-mediated HSV-Tk/GCV gene therapy for human malignant glioma
- 1 November 2001
- journal article
- clinical trial
- Published by Springer Nature in Cancer Gene Therapy
- Vol. 8 (11) , 843-851
- https://doi.org/10.1038/sj.cgt.7700382
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.Keywords
This publication has 17 references indexed in Scilit:
- HSV vector cytotoxicity is inversely correlated with effective TK/GCV suicide gene therapy of rat gliosarcomaGene Therapy, 2000
- A Phase 1-2 Clinical Trial of Gene Therapy for Recurrent Glioblastoma Multiforme by Tumor Transduction with the Herpes Simplex Thymidine Kinase Gene Followed by GanciclovirHuman Gene Therapy, 1999
- Molecular Evaluation of Biopsy and Autopsy Specimens from Patients Receiving in Vivo Retroviral Gene TherapyHuman Gene Therapy, 1999
- Bystander Effect-Mediated Therapy of Experimental Brain Tumor by Genetically Engineered Tumor CellsHuman Gene Therapy, 1998
- Evaluation of the Bystander Effect in Experimental Brain Tumors Bearing Herpes Simplex Virus–Thymidine Kinase Gene by Serial Magnetic Resonance ImagingHuman Gene Therapy, 1996
- Early postoperative magnetic resonance imaging following nonneoplastic cortical resectionJournal of Neurosurgery, 1996
- The role of cytokines in mediating the bystander effect using HSV-TK xenogeneic cellsCancer Letters, 1995
- The “Bystander Effect”: Association of U-87 Cell Death with Ganciclovir-Mediated Apoptosis of Nearby Cells and Lack of Effect in Athymic MiceHuman Gene Therapy, 1995
- The effect of thymidine kinase transduction and ganciclovir therapy on tumor vasculature and growth of 9L gliomas in ratsJournal of Neurosurgery, 1994
- Gene Therapy for the Treatment of Malignant Brain Tumors with In Vivo Tumor Transduction with the Herpes Simplex Thymidine Kinase Gene/Ganciclovir System. Iowa Methodist Medical Center, Des Moines, IowaHuman Gene Therapy, 1994