Scientists from the Cancer Research UK Institute for Cancer Studies at Birmingham University are using modified viruses, in a novel technique, to infect tumours so special drugs can be activated to seek out and destroy them.
In the new study they found the virus-based therapy could boost the effect of existing chemotherapy drugs. Researchers believe combining the two approaches could produce a potent treatment for tackling tumours in the future.
Study author Dr Daniel Palmer, from the Cancer Research UK Institute of Cancer Studies, says: “Viruses have evolved over millions of years to express many of the qualities required for the ideal anti-cancer weapon.
“A virus can target and infect very specific types of cell and we can harness this ability to attack tumours while leaving healthy tissue unharmed.”
The Birmingham team are using viruses in an innovative new approach called VDEPT (Virus Directed Enzyme Pro-Drug Therapy).
VDEPT works by infecting cancer cells with a genetically modified virus, designed to activate a harmless drug, called a pro-drug. When the infected cancer cells come into contact with the pro-drug, they start to convert it into its toxic form, which kills them. The beauty of this technique is that the pro-drug only becomes toxic in cancer cells because the virus infects them and not normal cells.
Researchers looked at how a type of VDEPT, involving a chemical called nitroreductase and pro-drug called CB1954, sends cancer cells to their death.
In the lab they injected ovarian cancer cells with a virus carrying a gene for nitroreductase and then added a pro-drug called CB1954 to the cells. CB1954 is transformed into its toxic form when it comes into contact with cancer cells that have been infected by the virus and are producing nitroreductase as a result.
The team found this type of VDEPT caused cancer cells to self-destruct by activating a particular component of the cell’s suicide machinery.
This suicide mechanism is similar to the way in which standard chemotherapies bring about cell death. So scientists decided to test combinations of the VDEPT and chemotherapy drugs, to see if they could improve the cancer killing effect.
Ovarian cancer cells were again infected with the virus and exposed to the pro-drug. But this time researchers also added one of the following chemotherapy drugs, cisplatin, 5-flurouracil, topotecan, doxorubicin, paclitaxel and gemcitabine to the cells.
They found the combination of 5-flurouracil and VDEPT could substantially enhance the anti-cancer effect, causing greater numbers of cancer cells to die than either of the drug or virus therapy alone.
However, combining VDEPT with the other drugs did not have the same result and in some cases there was even a negative effect.
Dr Palmer says: “Conventional chemotherapy is very efficient at killing cancer cells. But our study has shown combining particular drugs with a virus-based therapy in the lab can produce a deadlier and more potent effect.
“We now need to test which anti-cancer drugs perform well with this virus approach in a clinical setting.”
Professor Robert Souhami, Director of Clinical Research at Cancer Research UK says: “Harnessing viruses to target cancer cells is an exciting area of research.
“This study has shown that using a modified virus to activate a pro-drug is a potent and specific treatment in its own right but it can also complement conventional chemotherapies. It’s always important to develop novel methods for treating cancer and find ways to optimise existing ones.”
- British Journal of Cancer89 (5)