Vocimagene amiretrorepvec/flucytosine is an experimental

combination drug A combination drug or a fixed-dose combination (FDC) is a medicine that includes two or more active ingredients combined in a single dosage form. Terms like "combination drug" or "combination drug product" can be common shorthand for a FDC prod ...

involving a

gene therapy Gene therapy is a medical field which focuses on the genetic modification of cells to produce a therapeutic effect or the treatment of disease by repairing or reconstructing defective genetic material. The first attempt at modifying human DN ...

agent and a

prodrug A prodrug is a medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be used to improve how the drug ...

. It is a candidate drug to treat brain cancers. Vocimagene amiretrorepvec (also known as Toca 511) is a gene therapy agent, wherein the payload is a gene encoding

cytosine deaminase In enzymology, a cytosine deaminase () is an enzyme that catalyzes the chemical reaction :cytosine + H2O \rightleftharpoons uracil + NH3 Thus, the two substrates of this enzyme are cytosine and H2O, whereas its two products are uracil and NH3 ...

(CD) in a replicating, non-lytic retroviral vector.

Flucytosine Flucytosine, also known as 5-fluorocytosine (5-FC), is an antifungal medication. It is specifically used, together with amphotericin B, for serious ''Candida'' infections and cryptococcosis. It may be used by itself or with other antifungals for ...

(also known as 5-fluorocytosine, 5-FC, and Toca FC) is an antifungal drug. It is used in an extended-release formulation. Flucytosine is a prodrug of 5-fluorouracil (5-FU), a cancer drug. 5-Fluorouracil does not cross the

blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of ...

well, but flucytosine does. The combination drug was designed to be used after a brain tumor is removed surgically; vocimagene amiretrorepvec is intended to be injected into the tissues lining the hole where the tumor was (this region is called the

margin Margin may refer to: Physical or graphical edges *Margin (typography), the white space that surrounds the content of a page *Continental margin, the zone of the ocean floor that separates the thin oceanic crust from thick continental crust *Leaf ...

), 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. Flucytosine 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. By July 2017, the EMA had granted the combination priority review status, and the FDA had granted it

Breakthrough Therapy Designation Breakthrough therapy is a United States Food and Drug Administration designation that expedites drug development that was created by Congress under Section 902 of the 9 July 2012 Food and Drug Administration Safety and Innovation Act. The FDA's "br ...

and

FDA Fast Track Fast track is a designation by the United States Food and Drug Administration (FDA) of an investigational drug for expedited review to facilitate development of drugs that treat a serious or life-threatening condition and fill an unmet medical ne ...

designation for recurrent HGG, and an orphan designation for the treatment of glioblastoma. The combination is under development by Tocagen and as of July 2017 phase 2/3 trials were underway for recurrent

astrocytoma Astrocytomas are a type of brain tumor. They originate in a particular kind of glial cells, star-shaped brain cells in the cerebrum called astrocytes. This type of tumor does not usually spread outside the brain and spinal cord and it does not usu ...

and recurrent high grade

glioblastoma Glioblastoma, previously known as glioblastoma multiforme (GBM), is one of the most aggressive types of cancer that begin within the brain. Initially, signs and symptoms of glioblastoma are nonspecific. They may include headaches, personality ch ...

References

{{reflist Experimental cancer drugs