In May 2022 biotechnology firm Imugene and cancer research institute City of Hope commenced a clinical trial to examine the safety of infecting human beings with a virus designed to target and destroy cancer cells.
The virus, “Vaxinia”, had been shown to shrink cancerous tumours in colon, lung, breast, ovaries and pancreas in animal and preclinical trials. The virus hails from the same family as monkeypox, but has been genetically modified to infect, replicate in, and kill cancer cells while sparing healthy ones.
While Vaxinia is not the first oncolytic virus to reach this stage – in 2015 the US Food and Drug Administration (FDA) approved the first oncolytic virus therapy for melanoma, which used a modified herpes simplex virus – the latest trial has grabbed eyeballs globally.
Now the study aims to recruit 100 patients across approximately ten trial sites in the United States and Australia to gauge the safety of the virus and prove its efficacy.
But if the idea of injecting such a virus into your body is concerning, it may be pertinent to understand the science of how exactly oncolytic viruses operate and to acknowledge the scale of the problem that is cancer.
Dr Narendra Chirmule, former head of research and development at Biocon Ltd and author of the book Good Genes Gone Bad, spoke with Happiest Health about the significance of the trial; and why oncolytic viruses could become an important tool in our arsenal against cancer. Edited excerpts:
Happiest Health: Why is it hard to develop therapies against cancer?
Chirmule: Let me tell you a little story about cancer: let us say I have a wart on my skin. I go to my doctor, he looks at it, takes a biopsy and tells me, this is skin cancer. From a biology perspective, what happened in that tissue? How does cancer happen?
If I am exposed to the sun and UV light that induces a mutation in one of my cells, but my immune system is very competent and kills the mutated cell. Over a period, I’m constantly exposed to UV light and at some point one cancer cell escapes from being killed.
This one cell will stay dormant for many years until such time when your overall immune system gets compromised. Then that single cancer cell sitting dormant starts to grow. Initially it grows slowly as it needs oxygen, nutrients, blood and all kinds of things to grow. It gets these from your body, from nearby cells.
Then, the tumour grows into a mass of cells that don’t allow the immune system to come inside. They secrete these suppressive factors and create an environment where they can grow very well. This is the first time I see a wart on my hand. (By this point) I’ve had cancer for 20 years. I only see it on my skin, but it is invisible, and everywhere.
Happiest Health: What is the role of oncolytic viruses in the fight against cancer?
Dr Chirmule: In the last five to ten years, a revolution has happened in the field of immunology of cancer. The mechanism of how you can reactivate the immune system to start killing the tumour has been discovered – checkpoint inhibitors. These immune activators can go now and kill the tumour, but many tumours are not being cured because they are solid tumours that are very large.
This is because the tumour has created an environment where the immune system cannot enter. The immune checkpoint inhibitors can only activate the killing system if they are inside the tumour, and tumours prevent them from coming inside. If it turns out that your cancer has some immune cells in it, your cancer can be cured. But this happens in only 10 per cent of individuals.
[The mechanism of] a viral vector is like going into a fort and blasting a bomb. It enters the fort of the cancer cell, [replicates until the cell explodes,] allowing the immune cells to come in and start killing the tumour. A combination of viral therapy with checkpoint inhibitors [could be effective,] but checkpoint inhibitors by themselves are not very effective.
Happiest Health: Can the cancer cells develop countermeasures?
Dr Chirmule: The cancer cells will definitely develop them. Right now, we are blasting the cancer’s fort, so to speak. But [as to how the cancer will try to evade the immune system,] we can only speculate. But they’re not too many. Already a viral therapy drug is approved – T-VEC – and available in the market.
Happiest Health: Can T-VEC work against all cancers?
Dr Chirmule: In theory it can work in all cancers, but you must do the testing before you can use it.
Happiest Health: In oncolytic viruses, as they replicate is there any risk of copying errors that can creep in and make them perform differently than expected?
Dr Chirmule: The likelihood [of this happening] is very low because they are genetically engineered not to replicate and change. When you use oncolytic viruses, you’re not going to use them to kill every tumour, but just enough to activate the immune system. It is like giving a vaccine – you don’t give lots of virus, you just give a little bit. You’re giving the vaccine to activate the immune system so that the immune system can go now and kill all the cells.
Happiest Health: Can you explain the difference between oncolytic viruses and a vaccine-based virus?
Dr Chirmule: Oncolytic virus by definition is lytic – they lyse [kill] the tumour. Vaccines are just small portions of a virus. There are also no true cancer vaccines — unless you are talking about HPV and hepatitis viruses, which are known to cause cancer.
Happiest Health: How long do you think it will take for oncolytic therapies for different kinds of cancer to become readily available?
Dr Chirmule: Drug development has transformed after COVID-19. Prior to it, I would have said it would take at least ten years. Now I hope that people can do it in five years. Because what we’ve learnt from Covid is that there are many ways to improve drug development speed.
