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

• Published in: Cancer gene therapy Vol. 8; no. 11; pp. 843 - 851
• Main Authors: Floeth, F W, Shand, N, Bojar, H, Prisack, H B, Felsberg, J, Neuen-Jacob, E, Aulich, A, Burger, K J, Bock, W J, Weber, F
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.11.2001
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Brain - blood supply; Brain - pathology; Brain Neoplasms - diagnosis; Brain Neoplasms - therapy; Brain tumors; Bystander Effect; Encephalitis - diagnosis; Encephalitis - etiology; Encephalitis - immunology; Endothelial cells; Female; Ganciclovir; Ganciclovir - therapeutic use; Gene therapy; Genetic Therapy - adverse effects; Genetic Vectors; Glioma; Glioma - diagnosis; Glioma - therapy; Hemorrhage; Herpes simplex; Herpes simplex virus 1; Herpesvirus 1, Human - enzymology; Humans; Immune response; Inflammation; Magnetic Resonance Imaging; Male; Medical prognosis; Middle Aged; Necrosis; Neovascularization, Pathologic - diagnosis; Patients; Producer cells; Retroviridae - genetics; Suicide; Suicide genes; Thymidine; Thymidine kinase; Thymidine Kinase - genetics; Transfection; Transfection - methods
• ISSN: 0929-1903; 1476-5500
• DOI: 10.1038/sj.cgt.7700382

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.