Liposomal Gene Therapy with the Herpes Simplex Thymidine Kinase Gene/Ganciclovir System for the Treatment of Glioblastoma Multiforme

The experimental therapeutic approach is attracted to patients suffering from glioblastoma multiforme, a disease occurring with an incidence of 7-13 patients/100,000. The natural course of this disease is a median survival time of 4-6 months after diagnosis. Surgical resection and percutaneous radiotherapy increase the median survival to 10-12 months. The growth of intracerebral gliomas is characterized by two main features: besides a solid tumor, whose borders are macroscopically fairly delineated, glioma cells exhibit local invasion of various extension. Upfront treatment of gliomas (surgical resection or brachytherapy) is exclusively aimed to the solid tumor. Even though adjuvant strategies like radiotherapy or systemic chemotherapy are theoretically attracted against infiltrative cells, in most patients suffering from glioblastoma multiforme (WHO grade IV) tumor regrowth occurs 6-8 months after primary treatment within an area of 2-3 cm outside the solid tumor. One reason for the failure of systemically applied antineoplastic agents is the blood-brain barrier (BBB) or blood-tumor barrier (BTB). Due to their impermeable nature the passage of many drugs is blocked resulting in subtherapeutic tissue concentrations. The BBB is intact in peritumoral tissue located in the immediate vicinity of the solid tumor. Even in highly malignant brain tumors, the BTB is only inconstantly permeable. Thus, new strategies for the treatment of gliomas should ideally not only focus on solid tumor parts but also on infiltrative cells. On the technical side, methods have additionally to be integrated which may improve the delivery of active substances to the tissue.