In the flurry of bad news we have heard since the beginning of the year, you might have missed a good news story – a breakthrough by scientists at Southampton University which could fine-tune the body’s immune system into killing cancer cells.
The aim of the study was identify a way of turning immune therapy from promising theory into something which can benefit a greater pool of patients, By studying fibroblasts, a type of cell which surrounds tumours, the team had identified a variety which stimulates anti-cancer activity.
- New immunotherapy for women with advanced endometrial cancer
- Insights into female cancer
- Assessing and managing malignant melanoma in primary care
‘Our team has worked out what makes these cells form and can now do this in the lab,’ said Professor Gareth Thomas, Professor of Experimental Pathology at the University of Southampton. ‘Our next step is to work out whether we can use this information to develop a treatment that supercharges a patient’s response to cancer immunotherapy, giving them a better chance of beating this disease.’
Immunotherapy is a treatment that recruits the patient’s own immune system to fight cancer by amplifying it to recognise cancer cells as foreign agents. It is, surprisingly perhaps, a treatment with some heritage having been first used in 1891 by Dr William B. Coley in New York to shrink the tumours of a cancer patient by intentionally infecting them with streptococcal bacteria. But Dr Coley struggled to have his ideas adopted by the medical establishment, who dismissed them as ‘whispers of nature’. His theory faded to obscurity as cancer was largely treated with radiation, and then chemotherapy.
In the last decade however immunotherapy has been brought in from the cold and shown to work for cancer types such as melanoma as was seen in the case of Alex Green from Surrey who was diagnosed in 2012 and, before receiving immunotherapy, ‘expected to have died in 2019’ despite receiving both chemotherapy and radiotherapy.
Immunotherapy also has the potential to treat other forms of cancer such as endometrial cancer, as results from a clinical trial earlier in 2024 by the NHS found that 64% of patients who received immunotherapy in conjunction with chemotherapy had not seen their cancer progress past 12 months, in comparison to the 24% of patients who received chemotherapy alone.
How does immunotherapy work?
According to Dr Kat Thompson, Research Information Specialist at Cancer Research UK (CRUK), immunotherapy is an umbrella term for drugs, such as immune checkpoint inhibitors (ICIs), that battle cancer by ‘switching back on the immune system to recognise and kill cancer cells.’ Whilst our immune system technically has the aptitude to recognise cancerous cells in the body, cancer has the ability to trick the system to avoid being spotted. Therefore, immunotherapy teaches the body to bypass these tricks and attack cancer the same way it would fight a flu.
In terms of the sequence of prescription, immunotherapy would typically be used as a fallback after chemotherapy or as a combination of both in cases where traditional chemotherapy alone hasn’t worked. Considering that it is a less established treatment, it requires more technology to make and administer to patients, in turn providing a more targeted solution in comparison to chemotherapy’s generally untargeted nature. According to the NHS, immunotherapy works better for patients with melanoma in comparison to chemotherapy, with chemotherapy reserved for patients who cannot undergo other treatments.
However, while immunotherapy has been successful in melanoma cases, it still doesn’t work for every patient or every type of cancer. ‘Current immunotherapy used in the clinic only work for 10-15% of people,’ said Dr Thompson. ‘But there is a growing repertoire of types of immunotherapy that are becoming available.’
To find out why current therapies don’t work for some, and to develop more broadly applicable treatments, the UK government and industry partners have funded a research project, MANIFEST (Multiomic ANalysis of Immunotherapy Features Evidencing Success and Toxicity).
MANIFEST
Launched by the Francis Crick Institute in partnership with the Royal Marsden NHS Foundation Trust, MANIFEST is an observational study that will run over four years to further develop immunotherapy as a cancer treatment. The project is led by Samra Turajlik, Clinical Group Leader at the Francis Crick Institute, Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, and Associate Honorary Faculty at The Institute of Cancer Research, London.
‘In the last 10 years, we have made huge progress in the treatment of cancer with immunotherapy, but we are still underserving many patients due to treatment failure and side effects,’ Professor Turajlik said. ‘Ultimately, we want to speed up the delivery of personalised medicine for a disease that affects huge numbers of people across the UK every year.’
The project aims to predict how patients would respond to immunotherapy as well as its efficacy, by utilising biological samples from a predicted 3,000 patients in a search for available biomarkers that exist on the surface of cancer cells.
‘This is something that we can test within the patient,’ said Zayd Tippu, clinical research fellow at the MANIFEST project, and medical oncology trainee at The Royal Marsden NHS Foundation Trust and the Francis Crick Institute. The discovery of biomarkers mean that they can then be formally identified and used to assess whether a patient would benefit from immunotherapy treatment, as well as also signalling how someone will react to a drug. This could also potentially allow for the development of new treatments and vaccines, as well as discerning any potential side effects that could be experienced and investigating how to minimise their initial incidence rate.
How will the project work?
The project will begin by collecting tissue, blood and stool samples from 3,000 voluntary patients with melanomas, as well as renal, bladder, and breast cancer. The samples will then go through cellular and molecular profiling and will then be analysed to identify and ‘understand not only the tumour, but how it interacts with immune cells within its micro-environment,’ said Tippu, as well as potentially discovering new therapies for patients who haven’t responded to the initial immunotherapy.
The project will conclude in 2029 with the opening of their data for broader use, e.g. by academic institutions. The aim is to leave a legacy to allow for deeper investigation into more technology and diagnostic tools, as well as looking into the interactions between tumours and the surrounding environment.
What do we need to know?
A major concern for patients undergoing immunotherapy are the potential side effects. ‘These drug treatments don’t come without their risk of side effects or toxicities,’ said Tippu, who explained that some patients end up visiting the hospital because the side effects are ‘debilitating for patients and have significant effects on their morbidity.’
While discerning side effects is another goal of the MANIFEST project, some can already be observed in patients undergoing immunotherapy. According to CRUK, some of the side effects patients may experience whilst undergoing ICI immunotherapy are:
- skin problems (e.g. rashes, dry and itchy skin)
- diarrhoea
- inflammation of the digestive system
- fatigue
- feeling or being sick
- loss of appetite
- breathlessness and a dry cough, caused by inflammation of the lungs
- an allergic reaction causing shortness of breath, redness or swelling of the face and dizziness
- ICIs can also affect the liver, kidney, and thyroid, and as a result require regular blood monitoring to observe hormone levels.
But what should nurses take away from the development of these treatments? According to Macmillan Cancer Support, the daily duties of primary and secondary care nurses are similar to the duties regarding patients undergoing chemotherapy or other targeted treatments. However, the importance of education on the new therapies was emphasises, as ‘it is essential that all health care professionals in both primary and secondary care are aware of what side effects can present, so problems can be recognised early, and acted upon,’ said Rachel Bryce, Clinical Advisor at Macmillan Cancer Support. ‘With the increasing use of ICI in the majority of tumour sites, healthcare professional education needs to be a priority. Information on ICIs, National Guidance on Immunotherapy Toxicities, and educational resources on ICIs, can all be found on The Immuno-Oncology Clinical Network.’
Careful observation by nurses and other healthcare professionals is essential as ‘side effects can present months, and even years after an ICI has been stopped, and any part of the body, or system can be affected.’
What’s next?
‘We’re in the golden age of cancer research,’ said Dr. Thompson. For instance, she noted the current research focus on cancer vaccines, which ‘work in the same way other vaccines work against other diseases’ by recognising antigens present on cancer cells. Last year, the first lung cancer vaccination was administered in the UK at University College London Hospital (UCLH) to a patient with lung cancer as part of a clinical trial.
With the rapid continuation of research, the potential for widespread use of immunotherapy is set to increase across an expanded spectrum of cases. The ultimate completion of the MANIFEST and subsequent research projects, the broader efficacy of the treatment, as well as patient responses and side effects should be available for health and care professionals to familiarise themselves with. It is possible we are on the cusp of an exciting new chapter in healthcare.