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Hiding in plain sight: How we can use immune cells to deliver cancer-killing viruses to tumours

Jacob Smith
by Jacob Smith | Analysis

9 February 2023

13 comments 13 comments

A 3D illustration of virus particles
A 3D illustration of virus particles


What’s the first thing that comes to mind when you hear the word ‘virus’?  

If I had to guess, I would say you’re thinking about something negative. Most likely an illness of some kind. And, of course, that’s a reasonable answer.  

But what if I told you we can use viruses as a treatment for people with some types of cancer? 

There’s a special type of virus called an oncolytic virus that we can use as a type of immunotherapy. Oncolytic viruses are specially engineered to infect and replicate inside tumour cells, leaving normal, healthy cells uninfected. Once inside a tumour cell, the viruses cause the cell to die. 

And that’s not all. These viruses cause what’s called an immunogenic cell death. Put simply, this means that when the cells die, they trigger a response from the body’s immune system. 

By killing a tumour cell, the viruses help the body’s immune system to recognise tumour cells as foreign, because it sees the virus as foreign. That stimulates immune cells to attack and kill them. 

That might sound like it’s win-win, but there’s a catch. 

The immune system doesn’t just work with these viruses, it also works against them. If the body’s immune cells find them before they reach the tumour, they’ll destroy them, just as they would with any other foreign virus or bacteria in the body. 

For some cancers, like melanoma, this isn’t much of a problem. As these cancers are on the skin, the viruses can be injected directly into the tumour.  

But for other, less easily accessible tumours, this poses a big problem. The virus has to travel through the bloodstream to reach them and will encounter a lot of immune cells on the way.  

So, if we’re going to make oncolytic viruses a more effective treatment, we’re going to have to find a way to get them into tumour cells without immune cells getting to them. 

Luckily, researchers at the University of Sheffield, part funded by us, have found a way to do it.  

Ever heard of a Trojan horse? 

The big eater 

In this case, the horse is a type of immune cell called a macrophage. 

The job of a macrophage is to surround and kill any foreign microorganisms it finds in your body by engulfing and destroying them. In Greek, macrophage means ‘big eater’. And we can use that property to our advantage. We can put the virus inside a macrophage. 

“Macrophages are very happy to engulf and eat things, which makes them quite easy to infect with a virus,” says Dr Munitta Muthana, who leads the team. 

“But what also makes them great candidates for this is that you find a lot of macrophages in many tumours already. For example, some solid tumours have been reported to have around 50 to 80% macrophage content. 

“And unlike other immune cells, macrophages don’t just sit on the periphery or the outside of the tumour. They have this ability to penetrate quite deep into it.” 

So, in short, we can take macrophages from the blood of a person with cancer and infect them with the virus. Then, when we re-inject them into that person, the macrophage will take the virus straight into the tumour because that’s where it naturally homes in. 

But you might be wondering: how does the virus kill a cancer cell from inside a macrophage? 

The answer is it doesn’t.  

Because once the virus-containing macrophage gets into a tumour, the virus sees a better opportunity. 

A virus’s main purpose is to replicate as many times as it possibly can. It does that by infecting a cell and hijacking that cell’s own machinery to make copies of itself. That makes a tumour cell an ideal home for a virus.  

What better way to replicate than by hijacking a cell that is itself rapidly replicating? 

“With any cell that gets infected, eventually, the virus will leak out to try and find a better environment for survival,” says Muthana. 

“In this case, the virus will get into the tumour and think ‘I actually don’t want to be in this macrophage, I want to be in that tumour cell that’s rapidly dividing, because that means I can produce more progeny’.” 

The virus will leave the macrophage in favour of a tumour cell. And that’s when it will start to have therapeutic effect. 

Reaching the difficult targets 

Muthana’s team have been investigating the use of oncolytic viruses in several cancer types over the last few years. Now, they’ve turned their attention to cancers that have fewer current treatment options. 

Triple negative breast cancer (TNBC) is a type of breast cancer that makes up about 15% of breast cancers. It’s ‘triple negative’ because it lacks receptors for the hormones oestrogen and progesterone, and a protein called HER2. 

Without these receptors, hormone treatment and targeted therapies like Herceptin aren’t effective, meaning that overall, there are less treatment options for TNBC. 

And that brings us to the team’s recent research, published in Future Pharmacology, using oncolytic viruses against TNBC. 

They treated mice with TNBC with an oncolytic virus called HSV1716 in two groups. In the first group they administered the virus by itself, and in the second they administered it inside a macrophage.  

They found that in the mice that had been treated with the virus inside a macrophage, the growth of their tumour was slower, and they survived their cancer for longer than those in the other group.  

And that’s not all. Because the virus is protected by the macrophage, the team found that the viral load, meaning the amount of virus in a person’s blood, needed for the treatment to work was 100-fold less than when delivered without the macrophage.  

The presence of the macrophage also lessens off-target effects, as it carries the virus directly to the tumour without giving it the opportunity to infect other cells. 

The team have demonstrated that these viruses are effective at treating cancers like prostate cancer before, but this is the first time it’s been shown to work in TNBC. 

From cold to hot 

Another reason TNBC tumours are hard to treat is that they’re often what we call ‘cold’ tumours. This means they don’t have a lot of immune cells in and around them. That lack of immune cells, specifically cells called T cells, is the reason they don’t respond to immunotherapies. 

But oncolytic viruses could change that. 

“By attacking these cold tumours with a cancer-killing virus, you’re ‘waking up’ the immune system,” says Muthana. “And that can reprogram them and make them ‘hot’ tumours with lots of immune cells.  

“That could open the possibility of treating these patient groups with things like checkpoint inhibitors, which are very topical at the minute. There’s potential to look at combinations of these therapies for patients.” 

Oncolytic viruses could therefore represent a new treatment option for people with these types of hard-to-treat cancers. But more than that, they have the potential to make hard-to-treat cancers more receptive to existing therapies. 

So, while it will take some time before these therapies have been developed for use in humans, the future looks hopeful for oncolytic viruses. 

And ‘hope’ probably wasn’t the first thing that came to mind when you thought ‘virus’. 

Jacob

Dr Munitta Muthana

Dr Munitta Muthana

Dr Munitta Muthana is a group leader at the University of Sheffield. She has a long-standing track record in researching the development of cancer-killing viruses. Her team, Nanobug Oncology Sheffield (@Nanobug_shef), have created novel platforms to deliver viruses to tumours, successfully implementing cell delivery and magnetic guidance strategies utilizing soil bacteria.  

Currently, Dr Muthana’s laboratory is focused on protecting these viruses in the bloodstream and creating advanced nanomedicine platforms that enhance drug delivery to tumours while also preserving healthy tissue. 

    Comments

  • J R-H
    26 February 2023

    I was diagnosed with triple positive BC but was unable to have chemo / herceptin and had to stop hormone meds after 6 months. (That’s left me with wrecked tendons.) I believe that triple pos had worse outcomes than triple neg if treatments other than surgery cannot be undertaken. So would this treatment be available for someone like me? Are there are human trials requiring volunteers?

  • Ivan
    23 February 2023

    This is a very interesting subject and must offer hope to many people. I myself was diagnosed with bowel cancer and had an operation in August 2022 to remove part of my bowel which was succesful.
    Unfortunately the cancer had gone to my lung ( was going to have ablation ) but now to my liver as well. I am told that I cannot have an operation on my liver and can only be managed now by having a second treatment of 2 weekly chemo and tablets for 3 months.
    I am wondering if immunotherapy could be possible/appropriate for me at this stage.

  • Julie
    22 February 2023

    It is so inspiring to read about this research. I was diagnosed with breast cancer at the age of 33, prior to triple negative breast cancer being discovered. At the age of 59, I was diagnosed with triple negative in my other breast. I also have the BRCA1 gene. I remember saying to my breast surgeon that in my ignorance I had never heard of triple negative breast cancer and to be told it is the most aggressive type of breast cancer was naturally, both a shock and pretty scary. I have had amazing treatment both at Bart’s and the Royal London and to hear about new research for this type of breast cancer is truly amazing. I recently donated to cancer research in Stand Up for Cancer and also to a friend who is doing the fundraising steps in March. I myself have fundraised for Breast cancer now and I hope these contributions will further support the amazing research work being undertaken. Thank you.

  • Susan Conder
    22 February 2023

    Very interesting, thank you. I am having treatment for breast cancer, not sensitive to hormone treatment and had HER2. Have responded extremely well to chemotherapy, then a mastectomy and radiotherapy. Now nearly through injections of trastuzumab and Pertuzumab. Feel lucky to have had so much help aged 84!

  • Teresia
    22 February 2023

    Hi is Sacituzumba Govi. Part of this treatment?

  • reply
    Jacob Smith
    22 February 2023

    Hi Teresia,

    Thanks for your comment.

    No, this research focussed on oncolytic viruses, a type of immunotherapy. Sacituzumab govitecan is a targeted cancer drug. These work by ‘targeting’ those differences that help a cancer cell to survive and grow

    Best wishes,
    Jacob, Cancer Research UK

  • Douglas Clark
    22 February 2023

    Excellent work indeed. I’m wondering if any such work has been done on Glioblastomas….. I ask because my nephew has been diagnosed with this condition and prognosis is not good?

  • reply
    Jacob Smith
    22 February 2023

    Hi Douglas,

    We’re sorry to hear about your nephew’s diagnosis.

    There has been previous research into the use of oncolytic viruses to treat brain tumours, which showed some positive results. Equally, Dr Muthana’s team have been researching new ways to improve the success of chemotherapy in these cancers, though this doesn’t involve immunotherapy.

    If you have any questions about current treatments for glioblastoma, please feel free to reach out to Cancer Research UK’s nurses. You can call on freephone 0808 800 4040 between 9am and 5pm Monday to Friday. Or, to chat online with other people affected by cancer, you can join our fully moderated online community Cancer Chat at http://www.cancerchat.org.uk

    Best wishes,
    Jacob, Cancer Research UK

  • Rosemary Newill
    22 February 2023

    This could be fantastic news for my niece in Canada as she had 2 years of intensive chemo and radiotherapy for TNBC. She is cancer free now but great that should it re occur there is an alternative.

  • Mrs E M Bintliff
    22 February 2023

    Excellent news and easy to understand the article.
    Well done and Thank you!

  • CHRISTINA SHERWOOD
    22 February 2023

    I am so pleased you are trying to target triple negative breast cancer at last!
    Unfortunately it is too late to help my beloved sister who died last year, as the final stage was when it had spread to her liver, she bravely fought for 10 years. The only thing you can do is hope that one day something would be found to treat this evil disease. We were all living with the thought which new treatment was going to help my sister live a bit longer. Hopefully now more people will benefit from ongoing trials. The trogan horse is a good name to try to fool this evil, clever disease.

  • GEORGE BULLER
    22 February 2023

    As someone who is currently suffering from metastasized stomach cancer which is now in my bones and will shortly cause my demise, I find it hard to look at some of these potential treatments of the future without a touch of anger.

    I realise that awe can’t just crash on ahead Willy nilly with untried treatments, but sometimes I think we do waste too much time on research. Time that many cancer sufferers likely don’t have!

    It is my belief that we should offer more experimental treatments sooner rather than later and that by doing so we could perhaps speed up the acceptance/rejection of a new form of treatment. 😷

  • Sandra Tanner
    22 February 2023

    Wow the work you guys do is amazing.Real progress,huge congratulations

  • M Rowbotham
    22 February 2023

    I found this a very interesting subject

  • Paul Fairbrothet
    10 February 2023

    I can confirm that Imunotherapy works. I had advanced (stage4) Metastatic Melanoma. After a primary on my scalp and 4 metastases over 7 years treated by surgery and radotherapy my consultant decided immuno therapy was the best way to go. Started on Ipilimumab and Nivolumab for 12 weeks then just Nivolumab every 4 weeks.
    CT scans showed progressive small reductions in 3 small tumours over around years until it became ‘stable’ for a while. Then at 4 years I was told ‘no sign of cancer in your body’ Woo Hoo. Still being monitored. I have 6monthly CTs, one on this Saturday 🙂

    Comments

  • J R-H
    26 February 2023

    I was diagnosed with triple positive BC but was unable to have chemo / herceptin and had to stop hormone meds after 6 months. (That’s left me with wrecked tendons.) I believe that triple pos had worse outcomes than triple neg if treatments other than surgery cannot be undertaken. So would this treatment be available for someone like me? Are there are human trials requiring volunteers?

  • Ivan
    23 February 2023

    This is a very interesting subject and must offer hope to many people. I myself was diagnosed with bowel cancer and had an operation in August 2022 to remove part of my bowel which was succesful.
    Unfortunately the cancer had gone to my lung ( was going to have ablation ) but now to my liver as well. I am told that I cannot have an operation on my liver and can only be managed now by having a second treatment of 2 weekly chemo and tablets for 3 months.
    I am wondering if immunotherapy could be possible/appropriate for me at this stage.

  • Julie
    22 February 2023

    It is so inspiring to read about this research. I was diagnosed with breast cancer at the age of 33, prior to triple negative breast cancer being discovered. At the age of 59, I was diagnosed with triple negative in my other breast. I also have the BRCA1 gene. I remember saying to my breast surgeon that in my ignorance I had never heard of triple negative breast cancer and to be told it is the most aggressive type of breast cancer was naturally, both a shock and pretty scary. I have had amazing treatment both at Bart’s and the Royal London and to hear about new research for this type of breast cancer is truly amazing. I recently donated to cancer research in Stand Up for Cancer and also to a friend who is doing the fundraising steps in March. I myself have fundraised for Breast cancer now and I hope these contributions will further support the amazing research work being undertaken. Thank you.

  • Susan Conder
    22 February 2023

    Very interesting, thank you. I am having treatment for breast cancer, not sensitive to hormone treatment and had HER2. Have responded extremely well to chemotherapy, then a mastectomy and radiotherapy. Now nearly through injections of trastuzumab and Pertuzumab. Feel lucky to have had so much help aged 84!

  • Teresia
    22 February 2023

    Hi is Sacituzumba Govi. Part of this treatment?

  • reply
    Jacob Smith
    22 February 2023

    Hi Teresia,

    Thanks for your comment.

    No, this research focussed on oncolytic viruses, a type of immunotherapy. Sacituzumab govitecan is a targeted cancer drug. These work by ‘targeting’ those differences that help a cancer cell to survive and grow

    Best wishes,
    Jacob, Cancer Research UK

  • Douglas Clark
    22 February 2023

    Excellent work indeed. I’m wondering if any such work has been done on Glioblastomas….. I ask because my nephew has been diagnosed with this condition and prognosis is not good?

  • reply
    Jacob Smith
    22 February 2023

    Hi Douglas,

    We’re sorry to hear about your nephew’s diagnosis.

    There has been previous research into the use of oncolytic viruses to treat brain tumours, which showed some positive results. Equally, Dr Muthana’s team have been researching new ways to improve the success of chemotherapy in these cancers, though this doesn’t involve immunotherapy.

    If you have any questions about current treatments for glioblastoma, please feel free to reach out to Cancer Research UK’s nurses. You can call on freephone 0808 800 4040 between 9am and 5pm Monday to Friday. Or, to chat online with other people affected by cancer, you can join our fully moderated online community Cancer Chat at http://www.cancerchat.org.uk

    Best wishes,
    Jacob, Cancer Research UK

  • Rosemary Newill
    22 February 2023

    This could be fantastic news for my niece in Canada as she had 2 years of intensive chemo and radiotherapy for TNBC. She is cancer free now but great that should it re occur there is an alternative.

  • Mrs E M Bintliff
    22 February 2023

    Excellent news and easy to understand the article.
    Well done and Thank you!

  • CHRISTINA SHERWOOD
    22 February 2023

    I am so pleased you are trying to target triple negative breast cancer at last!
    Unfortunately it is too late to help my beloved sister who died last year, as the final stage was when it had spread to her liver, she bravely fought for 10 years. The only thing you can do is hope that one day something would be found to treat this evil disease. We were all living with the thought which new treatment was going to help my sister live a bit longer. Hopefully now more people will benefit from ongoing trials. The trogan horse is a good name to try to fool this evil, clever disease.

  • GEORGE BULLER
    22 February 2023

    As someone who is currently suffering from metastasized stomach cancer which is now in my bones and will shortly cause my demise, I find it hard to look at some of these potential treatments of the future without a touch of anger.

    I realise that awe can’t just crash on ahead Willy nilly with untried treatments, but sometimes I think we do waste too much time on research. Time that many cancer sufferers likely don’t have!

    It is my belief that we should offer more experimental treatments sooner rather than later and that by doing so we could perhaps speed up the acceptance/rejection of a new form of treatment. 😷

  • Sandra Tanner
    22 February 2023

    Wow the work you guys do is amazing.Real progress,huge congratulations

  • M Rowbotham
    22 February 2023

    I found this a very interesting subject

  • Paul Fairbrothet
    10 February 2023

    I can confirm that Imunotherapy works. I had advanced (stage4) Metastatic Melanoma. After a primary on my scalp and 4 metastases over 7 years treated by surgery and radotherapy my consultant decided immuno therapy was the best way to go. Started on Ipilimumab and Nivolumab for 12 weeks then just Nivolumab every 4 weeks.
    CT scans showed progressive small reductions in 3 small tumours over around years until it became ‘stable’ for a while. Then at 4 years I was told ‘no sign of cancer in your body’ Woo Hoo. Still being monitored. I have 6monthly CTs, one on this Saturday 🙂