An innovative new combination treatment that uses the measles virus to target cancer cells could significantly improve treatment for bowel and head & neck cancer, new research suggests.
A pre-clinical study found that exposing cancer cells to a genetically modified measles virus, in conjunction with radioactive iodide, radiation treatment and gene-targeting drugs, was much more effective than using any of the treatments separately.
Scientists at The Institute of Cancer Research, London, found that the quadruple treatment was able to deliver more radiation to cancer cells than radiotherapy alone while limiting the radiation dose to normal tissue.
The research was published this week in Radiotherapy & Oncology and was funded by The Institute of Cancer Research (ICR), Cancer Research UK, the NIHR Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and the ICR, and the Institut National du Cancer, Paris.
The ‘radiovirotherapy’ treatment - using viruses to deliver radioisotopes to cancer cells – is an innovative new way to treat cancer and could improve upon standard treatments for bowel and head & neck cancer.
About 50,000 people[1] in the UK are diagnosed with colorectal carcinoma (bowel cancer) or head & neck cancer every year, with bowel cancer the fourth most common cancer in the UK. Patients with these cancers are given radiotherapy treatment, but the amount of radiation that can be used to treat tumours is strictly controlled to avoid radiation damaging normal tissue.
Researchers used a cancer-targeting version of the measles virus known as NIS-expressing measles vaccine (MV-NIS) - genetically modified to express a gene called sodium iodide symporter (NIS). The protein that the NIS gene produces causes cancer cells to take up radioactive iodide, which can also be used to treat cancer.
Previous studies[2] have shown that oncolytic viruses – viruses that are able to selectively target and kill cancer cells, like MV-NIS – can be combined with radioiodide to tackle cancer more effectively than either treatment alone.
In the new study, ICR scientists combined four different treatments: the MV-NIS virus, radioiodide, radiotherapy and a drug called SAR-020106 – a drug that limits cancer cells’ ability to repair DNA damage, which was discovered by the CTU team at the ICR in collaboration with Sareum. They tested the treatments in head & neck cancer and colorectal carcinoma cell cultures to find which combinations delivered the most radiation to the cancer cells.
In all the cell cultures the researchers tested, they found that combining the MV-NIS virus with radiotherapy had a stronger effect than using either treatment separately. They found similar increases in treatment effectiveness when they combined the drug SAR-020106 with radiotherapy treatment, the MV-NIS virus with SAR-020106, and MV-NIS with radioiodide.
When they tested the combined treatment of MV-NIS, radiotherapy and SAR-020106 on mice with head & neck cancer tumours, they found the combination was much more effective than standard radiotherapy alone. Over half the animals survived to 60 days, compared with an average survival of 35 days for radiotherapy alone.
But the researchers saw the greatest improvement in survival when they added radiodide to the treatment mix. The new four-way treatment was particularly effective in mice with colorectal cancer tumours, with over 80% surviving to the end of the study.
Professor Kevin Harrington, Joint Head of the Division of Radiotherapy and Imaging at The Institute of Cancer Research and Honorary Consultant at The Royal Marsden said: “Measles is usually considered an enemy to human health, but here we’ve harnessed the virus to kill cancer cells. Each of the four treatments in this study can work on their own against cancer, but by using them together they add up to have an even larger effect, giving cancer a quadruple whammy.
“Three of the treatments used here are specifically selective for cancer but this is the first time they have been used together in this way. This study is a proof of principle that multi-layered, cancer-selective treatments can combine to give even better results. More research is needed to study this combined four-way treatment in a clinical setting, but it represents an attractive way to improve on what we can achieve with radiotherapy.”
Professor Alan Ashworth, Chief Executive of The Institute of Cancer Research, said: “Radiotherapy remains a vital part of doctors’ armoury against cancer, but if we’re to use it more effectively, we need to find ways of targeting radiation doses more precisely at tumours. This exciting study has shown in pre-clinical models that measles can form part of a combination treatment that attacks cancers while leaving healthy tissue alone. It’s an excellent example of how molecular medicine is being combined with traditional approaches to treatment as we seek new ways of improving patients’ outcomes from cancer.”
