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  • Writer's pictureAnson

Going viral...

Living with long-term cancer has led to me having numerous interactions with the Oracle Cancer Trust, the UK's leading national charity dedicated to head and neck cancer (HNC), so it was an absolute honour to be invited onto their Research and Funding Committee as a patient advocate. For many charities the pandemic has been extremely tough. Oracle have responded to these new challenges, first by finding out the opinions of over 200 healthcare practitioners, patients and caregivers, and second by figuring out how to address the deepening nature of inequalities in cancer diagnosis and care in our society.

So in a short series of posts, I want to look into what their new focus will mean for people living with / working on head and neck cancers. I’ll draw on some cutting edge developments in cancer research, as highlighted in Oracle’s Research and Innovation Evening, that was held in central London on the 4th July, and which exemplify Pillars 1 and 2 in the diagram above.

This week I'll look at the use of viruses to fight cancer, not cause it.

While in future posts I'll cover some of the latest developments in radiation & beam therapy, and then the strategies Oracle will use to help reduce inequalities in head and neck cancer awareness and treatment. For example, Oracle are leading a coalition of HNC organisations to “improve the care, experience and outcomes of all affected by Head and Neck Cancer in the UK”.

Oncolytic Virus Therapy

At the Research and Innovation Evening, my attention was particularly grabbed by a talk from Professor Kevin Harrington (Institute of Cancer Research) on the use of viruses to treat cancers when traditional immune checkpoint inhibitors (such as Pembrolizumab) are less effective.

For example, my tumours are “hot” (😉) i.e. are responsive to immunotherapy, but for many people their tumours are “cold”), so immunotherapy is not suitable for them.

We know that viruses can cause cancer, including my own HPV-related cancer, which I blogged about here. But can viruses also help to cure cancer?

In short yes. In fact, a branch of immunotherapy called oncolytic virus therapy (OVT) is devoted to it, harnessing viruses to infect and kill cancer cells. In the very briefest of summaries:

  • viruses can be genetically modified to boost the body’s own immune system to fight the cancer. The modified virus carries information that targets only cancer cells, and once the virus infects the patient, their immune system is stimulated to kill the cancer. The genetic modification also makes sure that the virus does not infect healthy cells in the body

  • After infection, the viruses also rapidly replicate within the cancer cells, causing those cancer cells to burst (or undergo lysis). When cancer cells burst they not only die, but now all those replicated viruses are released to spread further and infect other cancer cells, a bit like a chain reaction

  • Timings can be controlled, so that when cancer cells burst, they release enough cancer antigens to allow the body’s immune system to be activated, releasing immune cells called dendritic cells, to attack any remaining cancer cells nearby

  • If key cancer fragments/proteins reach the lymph nodes, and if T-cells can recognise these, T-cells and the body’s immune system will be further activated to destroy even more of the cancer cells

So really, the use of viruses as immunotherapy agents exerts a double or even triple whammy on cancer cells! And this is nicely summarised in the video to the right.

Increasingly, the combination of oncolytic virus therapy and immunotherapy (through check-point inhibitors including Pembrolizumab) are thought to hold great promise through encoding into the virus DNA checkpoint inhibitor antibodies to block PD-L1 or CTLA-4, allowing cancer cells to be “seen” once more by our own immune systems. A small trial published in 2017 for example, combined the first ever FDA-approved OVT (T-VEC) with Pembro, to treat metastatic melanoma. This resulted in increased infiltration of T-cells into tumours in over 60% of the patients. A key challenge remains in how to turn progress in using OVT in melanomas to other cancer types, including those associated with HPV, like my own. These and so many other examples, trials and mechanisms are reviewed by Professor Harrington and others in a recent 2019 Nature Reviews paper (although it is probably only understandable to cancer specialists!)

Oracle Cancer Trust have invested in pioneering early-stage OVT research projects, such as the use of reoviruses to kill cancer cells in a way that also makes them more “visible” to one’s immune system. In one funded study reoviruses have been shown to disrupt the production and transport of proteins in the cell’s endoplasmic reticulum (ER), a network of membranes within the cell itself. A bit like constipation (!) the modified virus causes the proteins to build up in the membranes to toxic levels, such that the cells are literally poisoned by their own protein build-up, and die.

From a personal perspective, the upshot of all this is, that if Pembro starts to become ineffective on my cancer, future use of oncolytic virus therapy may help to re-energise the drug's impact for a bit longer. For more reading on this topic, I thoroughly recommend this blog post by Joanne Duffy for the Institute of Cancer Research - it is a superbly written piece.

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