Oncolytics: The Cancer-killing Viruses

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A recent article published in the science media centre, STAT, tells the story of Stacy Erholtz, a 49 year old American lady, who had exhausted every treatment available in her fight against multiple myeloma. An uncommon type of blood cancer in which a group of plasma cells becomes cancerous and multiply.

In a last ditch attempt to tackle her worsening condition, Stacy was enrolled onto an experimental trial in which she would be injected with a measles virus, genetically engineered to target cancer. These reconditioned viruses, otherwise known as oncolytic viruses, are designed to locate, infect and destroy the cancerous cells, whilst sparing the healthy cells.

Thankfully, this is exactly what they did for Stacy. The very next day, the tumours that has plagued her body began to recede, and it wasn’t long after that that her doctors announced she was in complete remission.

I was yippy skippy. I felt like I was alive again.

Stacy Erholtz

However, despite this, and a smattering of other success stories, oncolytic viruses have not yet become a regular cancer treatment.

But, why not?

Well despite being the subject of over 100 clinical trials, the results have been..

Generally disappointing

Howard L. Kaufman, a surgical oncologist at Massachusetts General hospital

Only 7 of the 100 clinical trials have reached Phase III, with just one drug gaining regulatory approval from the FDA. Stacy’s case, it turns out, was just too unique.

However, complete remission doesn’t just happen by accident, there must be something to this, surely?

Well, yes, you wouldn’t be alone in thinking this. Experts in the field believe that the underwhelming results of the clinical trials may not be a symptom of poor potency of the cancer-killing viruses, but instead, from the design of the studies.

For example, in current cancer trials a key indicator of drug efficacy is tumour size. If the tumour shrinks, then that drug is deemed as likely to be successful in treating cancer. However, with oncolytic viruses, patients experience a phenomenon called ‘pseudo-progression’, this is where the virus-riddled tumour swells, before often collapsing and dying a few months later. This initial swelling of the tumours has been taken as sign of the progression of the cancer, rather than the regression, and has led to the results of some trials being misinterpreted, and the research halted.

Another aspect to consider is that usually patients are only allowed to enrol onto oncolytic virus trials once they have exhausted every other treatment option. In other words, patients are only allowed onto the trials once their immune system has already been subject to a battering by various different chemotherapy treatments. This is all before the trial has even begun. In one such study, an effective conclusion was unable to be drawn as the nine-patient cohort had undergone too varied a mix of therapies beforehand.

Follow-up blood work revealed that Stacy’s uniquely miraculous recovery was due to the fact that her previous treatments had wiped the measles-specific antibodies from her immune system. This cleared a path for the measles-based oncolytic virus to travel through her body, location, and killing, the cancerous cells.

When it comes to the further application of oncolytic viruses there are still questions to be answered. What is the ideal dosage? Should injection be directly into the tumour, or intravenously? And, which virus is the best for the job? If there was anything to be learnt from Stacy Erholtz’s case, it was that there is much to be excited about in the future for these cancer-killing viruses, however, these questions need to be answered.