Ascending dose trials of the safety and tolerability of Toca 511, a retroviral replicating vector encoding cytosine deaminase, in patients with recurrent high-grade glioma.

2101 Background: Patients with the most common and aggressive form of brain cancer, glioblastoma multiforme (GBM), have a poor prognosis and current treatments are only palliative. Gene therapy approaches using replication-deficient viral vectors have been investigated previously for GBM with limited efficacy, likely due to poor gene delivery throughout the tumor. Methods: Toca 511 is a novel retroviral replicating vector (RRV) that is engineered to deliver a modified cytosine deaminase prodrug activator gene (CD) selectively to cancer cells. In those cancer cells expressing the CD gene, the antifungal prodrug 5-FC is converted to 5-FU. We are currently evaluating the safety and tolerability of a single dose of Toca 511 administered by direct intratumoral injection to subjects with recurrent high grade glioma (rHGG). After a period of time during which the vector is allowed to spread through the tumor, the patient begins oral 5-FC which is repeated cyclically. Results: Three subjects have been enrolled in...