Oxford scientist Len Seymour is honing a radical new weapon in the long war to defeat cancer.
By John Garth
Fighting cancers without harming healthy tissues is a classic quandary. But now there may be a new weapon — and it means giving patients a virus.
Len Seymour, Professor of Gene Therapies in the Department of Oncology, is developing a new ‘virotherapy’ that uses an engineered virus to find and kill cancer cells but leave others unharmed.
The trick is to exploit the very thing that makes cancer cells so dangerous — their ability to self-replicate. The nature of cancer cells makes them an easy ride for viruses: their self-repair tools are faulty; they don’t self-destruct like normal cells; and they keep on reproducing themselves. ‘This gives a very high level of the therapeutic agent in the cancer and very little in normal tissues — to minimise toxicity,’ said Professor Seymour, who is a Supernumerary Fellow of Wolfson College.
The idea that viruses might kill cancer cells has long been entertained. The scientific literature has been peppered with reports of spontaneous tumour regressions happening in patients who are suffering from severe viral infections. But until genetic engineering took off, safety concerns made research problematic. ‘Progress has really accelerated in the last twenty years since we learned how to genetically modify viruses to make them effective anti-cancer agents but safe to normal tissues,’ said Professor Seymour. The result is a new generation of ‘oncolytic viruses’ — viruses that just love to infect and kill cancer cells.
Professor Len Seymour: ‘This approach provides incredible flexibility’
The virotherapy procedure would involve introducing the virus into the tumour, where it would do its work directly. But it would also be injected intravenously, so the virus could travel around the body and infect any cancer cells developing elsewhere. That would makes virotherapy a powerful tool against cancer’s insidious ability to spread unseen. The ideal scenario would be to use it when the cancer is at a very early stage.
The virus has a further trick up its sleeve too — it can turn the cancer cell into a drug factory, said Professor Seymour. ‘We can encode potent anticancer proteins, or “biologics”, within the viruses at the DNA level, so that the biologics are only produced at the tumour site. Effectively this turns the patient’s own cancer cells into little factories that produce the therapeutic biologic just where it is most needed.’
This startling possibility looks all the richer in the context of recent progress in cancer immunotherapy. Scientists now know that cancer cells escape detection by supressing the host’s immune system locally, within individual tumours. That opens up the potential to use oncolytic viruses as a delivery system to get immunotherapy to cancer cells throughout the body. Once there, it is hoped, they will be able to re-energise the body’s immune response against the cancer.
‘This approach provides incredible flexibility for targeted expression of pretty much any anticancer biologic,’ said Professor Seymour.
Currently a candidate virus, enadenotucirev, has been engineered and is undergoing Phase I clinical trials conducted by PsiOxus Therapeutics. Though it has been specifically tailored to target colorectal cancer cells, researchers are confident that it will also be effective against a range of other types — lung, kidney, breast, bladder.
Professor Seymour said: ‘We have been very lucky working with PsiOxus. They understand the value of scientific innovation and they can hugely accelerate our progress towards creating licensed medicines. Although you can have great new ideas in the University, it is very hard to undertake the clinical development unless you engage with a company that can access private finance.’
Virus digital image by Rost9 via Shutterstock; photo of Len Seymour by Sarah Stevenson; graphic by Len Seymour.