Killing cancer cells with a Trojan horse

1 in 2 people will develop some form of cancer during their lifetime. Scientists from Sheffield have developed a novel approach to killing cancer cells that reduces stress on the immune system.

Trojan horse

An exciting proposed venture from the Department of Oncology and Metabolism is using nanomaterials such as magnetic coatings to cloak cancer-killing viruses, preventing attacks from the immune system. Much like a Trojan horse, the coatings trick the immune system and allow doctors to guide the virus through the body directly to the tumour. 

Funded by Cancer Research UK and led by Principal Investigator Dr Munnita Muthana, an enterprising team at Sheffield are seeking to commercialise their research to bring it closer to patients with cancer.

According to Cancer Research UK, every two minutes someone in the UK is diagnosed with cancer.

Cancer occurs when a group of normal cells have abnormal growth and form a lump called a tumour (apart from blood cancers). If left untreated, the tumour can uncontrollably grow and spread to other parts of the body. 

Solid tumours can usually be surgically removed alongside other treatment methods such as chemotherapy and radiotherapy. While cancer survival in the UK is improving and has doubled in the last 40 years, there are different types of cancer drugs and drug combinations that all have individual side effects. 

Cancer such as Melanoma skin cancer spreads across the skin and cannot be removed with surgery. In this case, treatment options include a drug injection of a modified virus that infects and kills tumour cells. However, this method involves a high dosage of a virus that causes a reaction from the immune system leading to side effects such as blood clots, increased blood pressure and inflammation of organs such as the lungs. 

Senior Lecturer Dr Munitta Muthana, Dr Faith Howard and PhD student Natalie Winder set out to find a way to ensure the cancer-killing virus can survive in the bloodstream long enough to reach cancer cells intact, without being attacked by our body’s immune system.

Their paper has been awarded the Roger Griffin Prize for cancer drug discovery and the Sheffield team are expanding the range of tumours that can be tackled this way. The team are seeking to establish a spinout company based on their revolutionary technology with hopes of accelerating the treatment to reach patients.

“There’s a clear appetite for our offering and we’re working closely with the University’s Tech Transfer team to progress our proposed venture. As a team of three female co-founders, we’re proud of our achievements so far and have received a lot of interest and support from female venture capitalists” says Dr Faith Howard.

Understanding anti-cancer viruses

It is well-established that certain viruses have the ability to kill cancer cells. Known as oncolytic viruses, these viruses can be found naturally or modified in a laboratory to efficiently reproduce and attack cancer cells without harming healthy cells. For example, a modified herpes virus is now being used to treat people with certain types of skin cancer.

When this virus infects a cancer cell, the virus makes copies of itself until the cancer cell bursts open and dies. The dying cell releases materials that allow the cancer to be recognised and killed by the immune system.

The challenge is in ensuring the cancer-killing virus actually reaches its target. Current approaches require the virus to be delivered through surgery or injection but this only works for easily accessible tumours. Viruses travelling far in the bloodstream to tumour sites do not tend to survive as the immune system attacks them. In most cases, a very high dose of virus is needed which can cause significant side effects for the patient.

A proposed new venture from the University of Sheffield aims to take forward a novel approach to hide the oncolytic viruses from the immune system and only release the virus once they reach the cancer site.

Sheffield’s Trojan horse approach

Funded by Cancer Research UK and EU Horizons Europe the Sheffield team has found a solution to direct the virus quickly to a tumour. 

This revolutionary method coats the virus in protective magnetic particles allowing it to move freely in the body without being blocked by immune defences. Magnets are then placed over a patient's body to guide the therapy to the tumour. Similar to a Trojan horse, this approach hides the virus inside a nanoparticle only to be released once it reaches the tumour where it kills cells.

“Our research explored ways to target tumours while leaving healthy cells alone. This method of precision medicine has the potential to provide new treatments as well as repurpose drugs that are currently available but too harmful to be released ‘naked’ into the bloodstream. The coating technique allows any virus to enter the body at a much lower dose which significantly reduces side effects of a high dosage for patients” explains Dr Faith Howard.

“Currently, viruses need to be injected into the bloodstream at very high doses or directly into the tumour which is an invasive procedure. Our encapsulating technique means that the amount of virus used can be significantly reduced which will lessen the risk of side effects for the patient. The nanoparticle carrier can also be modified to work for any cancer” she adds.

As part of the University of Sheffield’s cancer research strategy, this research has been proven to reduce tumour size in pre-clinical prostate, brain and breast cancer models. The team hope that this novel approach could be used to fight a range of advanced cancers, which are typically hard to treat. 

Globally, many companies genetically modify viruses to target specific cancers but there is a huge barrier in delivering this virus directly to the tumour. There are widespread concerns about injecting viruses directly into the bloodstream but the encapsulating method developed by the team provides a safer and more effective solution to this problem.

With the support of Dr Jordan MacInnes from the Department of Chemical & Biological Engineering, the team have developed a prototype device that enables rapid large-scale production of these Trojan-horse platforms that is on track to outperform existing competition. 

The study represents a proof of concept but the small, portable device is at the centre of a proposed commercial venture led by the team with plans to share the technology with researchers and pharmaceutical companies worldwide.

An award-winning venture

Dr Faith Howard and team presenting
Copyright: The University of Edinburgh

The Venture Builder Incubator is a national programme delivered by the University of Edinburgh, in partnership with Barclays Eagle Labs and Cancer Research Horizons.

The programme provides PhD students and early career researchers from all over the UK with the skills and knowledge to maximise the impact of their research. It has attracted £1.8m in funding to date, allowing researchers to explore investment opportunities.

Faith and Natalie’s place on the programme was one of ten places sponsored by Cancer Research Horizons, the commercialisation arm of Cancer Research UK. 

The Showcase brought together 23 companies from all over the country.  The Sheffield pair were one of ten teams selected to pitch to a panel of judges and live audience with expertise across sectors, including entrepreneurs and investors in early-stage startups. The Showcase was the culmination of a four-month intensive programme, during which participants received training and advice to accelerate the translation of their research.  

Faith and Natalie were awarded the judges’ choice award for best pitch and received a cash prize of £4,000 to kick-start their aspiring new venture.

“The incubator was a great introduction to launching a business and has helped us attract interest from key stakeholders. We are currently using part of this prize money for market research before we launch and disseminate our product widely with academic and pharmaceutical industries” says Dr Faith Howard.

“There is a lot of potential to partner with pharmaceutical companies to use our platform technology to enhance the performance of active drugs available on the market. We can only get so far with pre-clinical modelling and funding so collaborations with larger companies will be a key step towards further clinical trials and reaching patients” she adds.

Looking ahead

The team is currently on the University’s Commercialisation Journey and to bring their product closer to market, are also taking part in the Innovation to Commercialisation of University Research (ICURe) led by the Biotechnology and Biological Sciences Research Council (BBSRC). The programme trains, funds, and supports research teams to validate commercial ideas. 

The team are engaging with stakeholders such as pharmaceutical and biotechnology companies and researchers to explore industries where the technology for encapsulation of sensitive biological agents can be used.

In years to come, Dr Faith Howard hopes the proposed new venture will bring about a non-invasive, kinder alternative to the standard of care for patients with cancer. The treatment has the potential to reduce pressure on the healthcare system as it would be delivered in outpatient clinics, providing more capacity for patients needing treatments that require an overnight stay.

As well as the anticipated fewer side effects due to a much lower dose of the virus, this standard of care has the potential to dramatically reduce patients’ tumours and improve outcomes of survival.

Our early tests have been encouraging but we’re now focusing on taking the next steps to bring this technique to a stage where it can be administered on humans. The rigorous market research we are currently conducting as part of the University of Sheffield's commercialisation journey, as well as on ICURe, will give our new venture the best chance of success and we're excited about the future.

Dr Faith Howard

Postdoctoral Research Associate in the Department of Oncology and Metabolism

This work is just one example of translating research within the University of Sheffield’s ambitious cancer research strategy. Through the new strategy, the University aims to prevent cancer-related deaths through ground-breaking research, leading to more effective treatments, as well as methods to better prevent and detect cancer and improve quality of life.

Written by Alina Moore, Research Communications Coordinator

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