Biology / Health / Science

Cancer-killing cold virus

Robert asked me to look into this BBC reportage of the common cold virus being used to attack bladder cancer cells, and working out quite successfully. The BBC report doesn’t have that many details: apparently the virus has been tested before (successfully? it doesn’t say, but presumably so) on skin cancer, and in this particular case it showed effects in all 15 patients who were treated with it. One showed complete remission, while the other 14 all had “evidence” that cancer cells had died. The BBC reportage does not state whether that was statistically significant, and I have to admit, on the surface I’m extremely wary about this one. A sample size of only 15 patients? Hmm. I wouldn’t expect the BBC to report on the statistics, but still, their absence leaves this very difficult to evaluate at all.

Fortunately, I managed to get my hands on the actual paper. Robert’s original question was about what the mechanism for this was — how could a cold virus have this effect?

First thing to understand is that there are several viruses that can cause the symptoms we lump together under the banner of ‘the common cold’: the most common are rhinoviruses and coronoviruses, but there are many others. This one is actually a coxsackievirus — the type that includes the cause of Foot and Mouth disease — and they tend to infect cells, reproduce, and then lyse the cell. That means that they break it open, spewing its contents and allowing the virus to spread, while killing the cell.

It’s a little misleading to say that the common cold is doing the cancer-killing: rhinoviruses are also lytic in the same way, which is probably why this virus can cause a similar illness when the upper airway is infected, even though it’s quite a different virus in reality. But coxsackieviruses aren’t even in the top five most common viruses that cause the common cold, so there’s no use sneezing on your cancer. What’s going on here is much more specific than the reporting makes it sound.

You can probably see already one way that infecting the cells with a virus that causes them to split open might work. Obviously, if it can be introduced directly to the cancer cells, and somehow be persuaded to only infect cancer cells, then the virus can kill those cells and destroy the tumour. That would be possible if there’s a way to engineer it so it can only bind to cancer cells, because that’s how viruses typically enter a cell. By one means or another, they bind to surface proteins on the cell, and are absorbed into it.

a) Viral entry (Fusion)

b) Viral entry (Endocytosis and lysis)

Diagrams showing viral entry by a) membrane fusion and b) endocytosis. The blue and yellow lines show bonds formed by the virus with the cell membrane.

Digging into the paper, that does seem to be what the study suggests as the mechanism for the success of this treatment. This particular coxsackievirus, CVA21, binds to cells expressing particular receptors. The patients were first treated with mitomycin C, which increased the expression of ICAM1 on cells, followed by infusion with the CVA21 virus. This can then bind to the right cells, allowing the virus to enter and lyse them.

There is a confounding factor here which makes me a little more wary about how well this mechanism works, and that’s the fact that mitomycin C is already active against tumour cells. It prevents further cell division, inhibiting further growth of the cancer. That could be causing some of the favourable results in the cases of these patients. Nonetheless, tumour necrosis (cell death) was specifically what they were looking for, and it was observed in the patients treated. Mitomycin C would only suppress further growth, rather than cause necrosis, suggesting that the responses are genuinely due to the activity of the CVA21 virus lysing cells.

It also sounds like the response has been limited in this study because an immune reaction is provoked, including an increase in checkpoint molecules which inhibit T-cells which would actually help in clearing the infected and cancerous cells. We already have well-tolerated checkpoint inhibitor drugs, which the authors of the study suggest adding in to help boost the efficacy of the therapy.

In conclusion, the mechanism makes sense and at this scale seems to have significant effects, but this is only a very small proof of concept trial. It needs to now go to successively larger trials to evaluate safety and ascertain the effective dosage, and modifications like the addition of checkpoint inhibitors definitely need to be followed up on. It could be that the effects seen in this extremely small cohort are exceptional… but it could also be that with the addition of a checkpoint inhibitor, this therapy will be a boon for those with bladder cancer. It’s early, but the principles and early results seem sound!

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