Convection-enhanced delivery to achieve widespread distribution of viral vectors: Predicting clinical implementation

Convection-enhanced delivery (CED) has been introduced to overcome the inability of many pharmacological agents to cross the blood-brain barrier, making these agents potentially effective in situ and suitable for the treatment of brain disorders. To achieve CED, drugs are pumped continuously through stereotactically placed catheters directly into the brain, or into or within the vicinity of a tumor mass. This medical technology has been applied to the local delivery of small-molecule drugs, including standard chemotherapeutics, and novel experimental targeted drugs, including targeted cytotoxins. When administered by an experienced clinician, the CED of a molecularly targeted cytotoxin has resulted in a significantly better outcome in patients with recurrent glioblastoma multiforme (GBM). More recent gene therapy clinical trials have also demonstrated that such treatments impact on the course of the disease when administered using CED. The use of CED to administer gene therapy for brain neoplasms may improve the efficacy of this treatment. However, CED is under development, and issues such as the type of catheters to use and their placement, as well as the pharmacological formulation and stability of drugs or vectors, are being studied to achieve efficacious delivery into the desired regions of the diseased brain. This review discusses the use of CED to deliver gene therapy for brain tumors, particularly gliomas, such as GBM.