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Oncolytic viruses

Oncolytic viruses infect tumour cells, where they can either kill the cell directly or act as a flag to the immune system.

What is an oncolytic virus?

Viruses can infect and kill cells. Some naturally occurring viruses, as well as viruses that have been altered in the lab, infect and kill cancer cells. These are known as oncolytic viruses.

Along with killing the cells directly, the viruses can also alert the immune system to attack the cancer cells.

Reovirus

The reovirus is an example of an oncolytic virus.

The reovirus is a naturally occurring and mostly harmless virus, which has previously been shown to effectively home in on cancer cells, while often leaving healthy cells alone. The reovirus also has the ability to cross the blood-brain barrier.

In an early study, the reovirus was injected via a drip into the bloodstreams of nine people before surgery for a brain tumour. Samples taken during their operations showed evidence that the virus had reached the tumour.

The samples also showed that those who received reovirus had higher levels of interferons - proteins that 'switch on' the body's immune system.

Our immune systems aren't very good at 'seeing' cancers – partly because cancer cells look like our body's own normal cells, and partly because cancers are good at telling immune cells to turn a blind eye. But the immune system is very good at seeing viruses, therefore more effective at seeking out tumour cells that contain a virus.

The reovirus is being studied for use on high grade gliomas, including glioblastoma.

Toca 511/Toca FC

A phase 2/3 clinical trial is being planned that will evaluate the effectiveness of using a combination drug involving Toca 511 and Toca FC for newly diagnosed glioblastoma. The combination drug will be used alongside the usual treatment –temozolomide and radiotherapy.

The trial will be co-ordinated by the gene therapy company Tocagen. As yet, it's not yet recruiting and locations are yet to be announced, but are likely to be mostly in the US.

It should be noted that a recent Phase 3 trial using Toca 511 and Toca FC in recurrent glioblastoma failed to increase survival. This led to the Toca 5 trial being discontinued.

How do Toca 511 and Toca FC work?

Toca 511 is given to the patient first. It is given by injection, at the time of surgery, into the cells lining the edge of the site where the tumour was removed from.

It has been designed to seek out tumour cells and infect them. It can do this because it is a virus that targets rapidly dividing cells, such as tumour cells. It carries with it a gene that makes the tumour cell produce an enzyme called CD. Each tumour cell it infects is given a copy of the gene and begins to produce CD.

Toca FC is then given to the patient in the form of a tablet. Toca FC is carried in the bloodstream, across the blood-brain barrier and enters brain cells. When it comes into contact with CD, which is only produced by the tumour cells, Toca FC is converted into an anti-cancer drug (called 5-FU) that kills the tumour cell from the inside.

Finally, the dying tumour cell releases certain chemical signals, which activate the body’s natural immune system to help kill more tumour cells.

It is important to know that this form of 'gene therapy' does not make any permanent changes to the tumour DNA, nor to the patient's healthy DNA. It's simply using a virus to deliver a gene into the tumour location that activates Toca FC.

Can I receive this treatment?

The short answer is "not yet". 

According to clinicaltrials.gov, updated on 24 October 2019, the trial is not yet recruiting and locations have not been announced. As of 28 October 2019, the Tocagen website says that the trial “is expected to begin enrollment in the second half of 2019”.

If you have further questions, need to clarify any of the information on this page, or want to find out more about research and clinical trials, please contact our team:

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