Tocagen Treatment: Toca 511
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Disclosure: Tocagen, Inc is a sponsor of this website

Toca 511 & Toca FC

Updated 8/20/2012 by Al Musella, DPM

This is a very exciting new experimental gene therapy treatment for high grade brain tumors. The basic concept is that a virus (Toca 511) is injected into the tumor. This virus was designed to infect only the brain tumor cells and leave the normal cells alone. When it infects a cell, it adds a gene to the cell which encodes for an enzyme that can convert an antibiotic drug (Toca FC) into a toxic chemotherapy (5-FU), selectively in the tumor. This drug (Toca FC) is given orally every few weeks, and it kills the tumor cells that have enough copies of this enzyme to convert Toca FC to 5-FU. The tumor cells that are infected but don't have enough of the enzyme act as a reservoir - they start the process over again - spreading the infection for a few more weeks, and these cycles are repeated over and over again until the entire tumor is potentially gone.


This is a presentation from our brain tumor patient conference on Tocagen Toca511 & Toca FC:


NBC affiliate features Cleveland Clinic patient in Tocagen's investigational trial for brain cancer



Status: this treatment is only available in clinical trials right now (as of 8/20/2012). There are 2 clinical trials:
  1. A Study of a Retroviral Replicating Vector Administered to Subjects With Recurrent Malignant Glioma (NCT01156584): this is for people with recurrent high grade glioma, including glioblastoma multiforme, anaplastic astrocytoma, high grade oligodendrogliomas and others. For details, click HERE
  2. Study of a Retroviral Replicating Vector to Treat Patients Undergoing Surgery for a Recurrent Malignant Brain Tumor (NCT01470794): this is similiar to the above trial, but is for people who have chosen to have surgery to remove their tumor. For details, click HERE

How does Toca 511 differ from previous gene therapies? Gene therapy uses a virus to insert a gene into cells. Previous versions of gene therapy used viruses that were not able to replicate, so it depended on getting enough of the virus in contact with all of the tumor cells, at one time, or with a few repeated attempts. This actually worked well in small lab animals but in people, the brain is just too large and there are tumor cells that spread away from the main tumor mass. These therapies helped advance the understanding of using viruses and gene therapies to fight brain cancer, but showed disappointing efficacy results.
With Toca 511, the virus does replicate inside the body. It can only infect and replicate in dividing cells. The virus was designed so that not only does it requre dividing cells (tumor cells divide much more frequently than the normal cells in the body), but it is controlled by the body's innate immune system. There is a locally depressed immune system in the area of brain tumors which allows the virus to escape the body's natural immune system. This creates the situation where the virus selectively infects tumor cells and not normal cells. Since not all tumor cells are dividing at any one time, it also allows for the infection of tumor cells over time - many months.

What is Toca FC? Toca FC is a new formulation of an old antibiotic drug (flucytosine). Flucytosine was approved to treat fungus infections in the brain and is still used today. This drug kills selectively fungus but not human cells. By itself, flucytosine is generally well tolerated. But inside fungus cells, a yeast enzyme, cytosine deaminase, converts the flucytosine to 5-fluorouracil (5-FU), which kills the fungus cells. Humans do not have this enzyme. The absence of cytosine deaminase in human cells allows selective effects on fungal cells. Toca 511 inserts the gene that codes for cytosine deaminase into tumor cells, so the tumor cells can also convert the flucytosine to 5-FU.
The new formulation of Toca FC is an extended release formulation of flucytosine so the blood concentration of the drug is steadier. With the older immediate release version of flucytosine, some people developed nausea right after taking it - along with other toxicities. The new version, Toca FC, has been well tolerated in brain cancer patients to date and there have been no drug related serious side effects reported.

Does it work? Is it a cure for brain tumors? It is too early to tell if it will be a cure for human brain tumors, but the preclinical data are promising. Many other treatments are not shooting for a cure - they are trying to extend life by a few months. In lab animals, many mice were cured of the brain tumor with Toca 511 and Toca FC. See the links to articles below for details.

Should I worry that the virus will infect my whole body? To date, there have been no safety concerns in Tocagen's clinical trials however, this was my first question to the people who invented Toca 511. It does sound scary - injecting a virus into your brain. Aside from the property of the Toca 511 virus to only infect dividing cells that have a decreased immunity, the inventors built in a fail safe: they made the virus very sensitive to the oral antiviral drugs. IF something bad happens, they can clear the body of the virus with oral antiviral.

What does Toca 511 / Toca FC cost? This treatment is in investigational trials,a nd is not yet commercially available. Inside the trial, the Toca 511 & Toca FC are provided without charge. Other costs associated with it's use - such as any need for surgery or other drugs, may be covered by your insurance. Ask the doctors about any possible costs, but in general, cost is not an issue in these trials.

How do I join the trial? Just call the center closest to you (see below) and tell them you are interested in the Toca 511 trial!

These doctors are involved in the Tocagen Toc 511 & Toca FC trial for people who do NOT need to undergo surgery

StateCityHospitalDoctorPhoneEmail

These doctors are involved in the Tocagen Toc 511/ Toca FC trial for people who need to undergo surgery

StateCityHospitalDoctorPhoneEmail


Articles About Tocagen Toca 511/ Toca FC

  1. Scientific American Article about Tocagen

  2. News Article about this treatment!

  3. Perez O. and Logg C. et al. Design and Selection of Toca 511 for Clinical Use: Modified Retroviral Replicating Vector With Improved Stability and Gene Expression. Mol. Ther. 2012; May, Advanced Online Publication.

  4. Logg, C. R. et al. (2012) Chapter 11: Retroviral Replicating Vectors in Cancer, in Friedmann T. (ed) Gene Transfer Vectors for Clinical Application,Academic Press,199-228. [Note: not free]

  5. Ostertag D. et al. Brain tumor eradication and prolonged survival from intratumoral conversion of 5-fluorocytosine to 5-fluorouracil using a nonlytic retroviral replicating vector. J Neurooncol. 2012;14(2):145-159. Supplementary Data


Disclosures:
  1. Tocagen, Inc is a sponsor of our organization
  2. The Musella Foundation is a sponsor of the Tocagen trial - See http://virtualtrials.com/news3.cfm?item=5314



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