Chemistry:Toca 511 and Toca FC
Toca 511 and Toca FC is a combination drug involving a gene therapy agent and a prodrug. It is a candidate drug to treat brain cancers. Toca 511 (vocimagene amiretrorepvec) is a gene therapy agent, wherein the payload is a gene encoding cytosine deaminase (CD) in a replicating, non-lytic retroviral vector.[1]
Toca FC is an extended-release formulation of the antifungal drug, 5-fluorocytosine, which is a prodrug of 5-fluorouracil, a known cancer drug. 5-fluorouracil does not cross the blood-brain barrier well, but 5-fluorocytosine does.[1]
The combination drug was designed to be used after a brain tumor is removed surgically; Toca 511 is intended to be injected into the tissues lining the hole where the tumor was (this region is called the margin), where the virus replicates only in cells that are dividing - in other words, cancer cells left over in the margin and immune cells that are present. 5-fluorocytosine is then administered to the person, and is converted to 5-fluorouracil in those cells by CD expressed by cells that had been infected with the gene therapy vector.[1]
By July 2017 the EMA had granted the combination priority review status, and the FDA had granted it Breakthrough Therapy Designation and FDA Fast Track designation for recurrent HGG, and an orphan designation for the treatment of glioblastoma.[2]
The combination is under development by Tocagen and as of July 2017 phase 2/3 trials were underway for recurrent astrocytoma and recurrent high grade glioblastoma.[2]
References
- ↑ 1.0 1.1 1.2 Strebe, JK; Lubin, JA; Kuo, JS (December 2016). ""Tag Team" Glioblastoma Therapy: Results From a Phase 1 Trial of Toca 511 and 5-Fluorocytosine for Recurrent High-Grade Glioma.". Neurosurgery 79 (6): N18–N20. doi:10.1227/01.neu.0000508605.38694.fd. PMID 27861411.
- ↑ 2.0 2.1 "Vocimagene amiretrorepvec-flucytosine gene therapy - Tocagen" (in en). AdisInsight. http://adisinsight.springer.com/drugs/800032273. Retrieved 29 August 2017.
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