Image: Radiotherapy machine at The Royal Marsden Hospital Credit: Jan Chlebik, ICR
Since its inception, immunotherapy has made waves and revolutionised cancer treatment for some patients, thanks to its unique mode of action that primes their immune systems to fight the disease. It’s a complicated process that doesn’t work for everyone, however, leaving many people by the wayside when standard therapies have failed.
But combining immunotherapy with other treatments, such as radiotherapy, could help expand the number of patients who benefit. If we could understand how different treatments can work in combination with each other to stimulate an immune response, those cancer patients for whom immunotherapy initially failed to work may still be able to get the most out of this innovative approach.
Dr Erik Wennerberg’s research at The Institute of Cancer Research entails exactly that. He heads the Radiation-enhanced Immunotherapy Team, which is interested in how radiotherapy can be used to bolster the effects of immunotherapy by looking at its effects on tumours – offering a possible lifeline for patients who don’t respond or whose tumours become resistant.
Natural next step
Radiotherapy involves subjecting tumours to high-energy beams of radiation, such as X-rays, to either kill cancerous cells or keep them in check by damaging the tumour DNA. It’s a promising candidate for developing this combined approach as it can not only kick-start the immune system into action, but also trigger suppressive mechanisms in the tumour, revealing a host of potential new targets for therapy.
“Radiotherapy – being an established treatment for decades and already known to trigger certain types of immunogenic cell death – is a natural next step when looking at this combination therapy,” says Dr Wennerberg.
He first became interested in how radiation affects tumours as a postdoctoral researcher at Weill Cornell Medicine in New York, which spurred him to start looking at ways to combine radiotherapy and immunotherapy in his research. He joined the ICR’s Division of Radiotherapy and Imaging in July 2020. Here, his main focus – and favourite aspect of his work – is how tumours become resistant to immunotherapy in the first place, either by hiding from the patient’s immune system or directly shutting it down.
“There are so many pathways that we still don’t know the biology behind, so we need to get a deeper understanding of these mechanisms and the effects on tumours before going into clinical studies,” says Dr Wennerberg.
Pre-clinical animal models are crucial for simulating and studying these kind of effects, as well as the expertise of scientists to understand how these factors slot together to cause or prevent an immune response. Our new Centre for Translational Immunotherapy (CTI) is a virtual platform that brings together researchers and clinicians from the ICR and The Royal Marsden NHS Foundation Trust who work in this sphere. It allows them to bolster their vital work in immunotherapy by facilitating communication and collaboration with different teams across the ICR.
Dr Wennerberg explains: “The CTI is a platform to promote progression and knowledge-sharing, to have a dialogue within the ICR and The Royal Marsden and potentially across other institutes – to promote translational immunotherapy research, and not necessarily just among immunologists. That’s the main goal of this exciting initiative.”
Spotlight on radiotherapy
And where radiotherapy and immunotherapy are concerned, the door is open to new discoveries. Despite radiotherapy being generally kinder for patients than chemotherapy – focal radiotherapy only targets a specific part of the body, resulting in fewer side effects – it is sometimes underappreciated as a therapeutic avenue. This is largely down to a lack of investment and public awareness of its benefits, despite radiotherapy being used in around 40 per cent of cancer cures.
To address this investment gap, the ICR has recently launched its position statement on radiotherapy – calling for improved access to new radiotherapy technologies, so that the latest advances in the field can play a key role in clearing the build-up of cancer research during the Covid-19 pandemic.
What’s more, there’s still much to learn about how radiotherapy works on tumours and interacts with components of immunotherapy, such as drugs or antibodies, to initiate an immune response.
But it isn’t the only way to do so. Oncolytic peptides are small molecules that can have a deadly effect on tumours and are getting attention for their immunogenic properties. And it turns out that injecting them into patient’s tumours provides a similar boost to their immune system as using radiotherapy. That’s why Dr Wennerberg is interested in both approaches. “They essentially have the same outcome of delivering that initial trigger that can spark an immune response against a patient’s tumour,” he says.
Both oncolytic peptides and radiotherapy are being investigated in ongoing clinical trials for how well they can be used in combination with immunotherapy. It’s likely that these approaches could work on many cancer types, though Dr Wennerberg’s focus currently lies with lung cancer and, to a lesser extent, breast cancer.
An exciting time
The timing of Dr Wennerberg’s joining of the ICR during Covid-19 restrictions has meant that his experimental work has unfortunately, but inevitably, had to take a backseat in his time here. As facilities begin to reopen, he says he’s looking forward to getting back into the swing of laboratory work. One experiment he is setting up involves using cell lines to investigate how irradiated tumour cells release ‘danger signal’ molecules, such as adenosine triphosphate (ATP), which carries energy in cells and is released in stressed or dying cells. These signals can serve a dual function by both triggering and suppressing an immune response.
The initiatives taking place at the ICR, such as the CTI, play a central role in facilitating this crucial research. “The ICR is a great place to work because there’s such a broad expertise and knowledge across all research divisions,” says Dr Wennerberg. “So many of our clinicians have an interest in immunology research, which is an ever-expanding field. It’s a very exciting time to be working here.”
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