Scientists have equipped a virus that kills carcinoma cells with a protein so it can also target and kill adjacent cells that are tricked into shielding the cancer from the immune system and supplying it with growth factors and nutrients.
Researchers at the University of Oxford said it is the first time cancer-associated fibroblasts within solid tumours have been specifically targeted in this way.
They believe if further safety testing is successful, the dual-action virus – which they have tested in human cancer samples and in mice – could be tested in humans with carcinomas as early as next year.
Currently, any therapy that kills the “tricked” fibroblast cells may also kill fibroblasts throughout the body – for example in the bone marrow and skin – and cause toxicity.
In this study, published in the journal Cancer Research, scientists used a virus called enadenotucirev, which is already used in clinical trials for treating carcinomas.
It has been bred to infect only cancer cells, leaving healthy cells alone.
They added genetic instructions into the virus that caused infected cancer cells to produce a protein called a bi-specific T-cell engager.
The protein was designed to bind to two types of cells and stick them together.
In this case, one end was targeted to bind to fibroblasts. The other end specifically stuck to T-cells – a type of immune cell that is responsible for killing defective cells.
This triggered the T cells to kill the attached fibroblasts.
The virus targets carcinomas, which are the most common type of cancer and start in cells in the skin or in tissues that line or cover internal organs, such as the pancreas, colon, lungs, breasts, ovaries and prostate.
Dr Nathan Richardson, head of molecular and cellular medicine at the Medical Research Council (MRC), which was involved in funding the study, said: “Immunotherapy is emerging as an exciting new approach to treating cancers.
“This innovative viral delivery system, which targets both the cancer and surrounding protective tissue, could improve outcomes for patients whose cancers are resistant to current treatments.
“Further clinical studies will be crucial to determine that the stimulation of the patient’s immune system does not produce unintended consequences.”
The team tested the therapy on fresh human cancer samples collected from consenting patients, including solid prostate cancer tumours that reflect the complex make-up of real tumours.
They also tested the virus on samples of healthy human bone marrow and found it did not cause toxicity or inappropriate T-cell activation.
Dr Kerry Fisher, from the University of Oxford’s Department of Oncology, who led the research, said: “Even when most of the cancer cells in a carcinoma are killed, fibroblasts can protect the residual cancer cells and help them to recover and flourish.
“Until now, there has not been any way to kill both cancer cells and the fibroblasts protecting them at the same time, without harming the rest of the body.
“Our new technique to simultaneously target the fibroblasts while killing cancer cells with the virus could be an important step towards reducing immune system suppression within carcinomas and should kick-start the normal immune process.
“These viruses are already undergoing trials in people, so we hope our modified virus will be moving towards clinical trials as early as next year to find out if it is safe and effective in people with cancer.”
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