Dynamite for Cancer Cells
A virus to cure cancer? It's possible! Some viruses can infect cancer cells specifically, and cause them to burst. These are known as oncolytic viruses.
Oncolytic viruses infect tumour cells, where they can either kill the cell directly or act as a flag to the immune system.
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.
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.
Toca 5 is a clinical trial to evaluate the effectiveness of using Toca 511 and Toca FC as a two-part treatment for recurrent high grade gliomas – glioblastoma and anaplastic astrocytoma. The trial is being performed in the USA, Canada and South Korea by the gene therapy company Tocagen. It's expected to be completed by the end of 2019 and is not currently recruiting.
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, every day for 7 days. This starts 6 weeks after surgery and is repeated every 6 weeks. 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 5-FU, an anti-cancer drug 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 is just using a virus to deliver a gene into the tumour location that activates Toca FC.
The short answer is "not yet". The Toca 5 clinical trial still needs to complete phase 3, which will take another 3-5 years. After the phase three clinical trial is completed, the Toca 5 treatment will then only be readily available to patients after it has been assessed and approved by various national health systems – in the UK, this means by the NHS. Unfortunately, this process can take several years.
There is good news though. Due to the positive effect the Toca 5 treatment has been having on overall survival, Toca 511 and Toca FC have been granted orphan status and PRIME designation by the EMA (European Medicines Agency) and Breakthrough Therapy Designation by the FDA (Food & Drug Administration) in the USA. These are schemes to bring promising treatments for rare diseases to the market more quickly, so they can be used by more patients.
Occasionally people can access promising drugs that are being investigated via a scheme called compassionate use or expanded access. However, Tocagen’s current policy is to focus on the required clinical trials, which means they are not supporting an expanded access program at the moment.
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