Författare: Justin Stebbing Professor of Biomedical Sciences Anglia Rusk

In the battle against diseases, the human body boasts an intricate defence network capable of identifying and neutralising threats – the immune system.
It serves as a guardian, constantly patrolling the body to keep it safe from invaders like bacteria, viruses, and even cancer cells.

Scientists are harnessing the power of the body’s natural defence mechanism to develop immunotherapy, revolutionising the landscape of medical treatment. It enhances, redirects, or restores the body’s immune response to recognise and eliminate abnormal cells, such as cancer cells or those responsible for autoimmune diseases like multiple sclerosis, rheumatoid arthritis and type 1 diabetes.

Immunotherapy, however, is expensive. So, chemotherapy and radiation therapy are still the primary cancer treatments for most patients. But these conventional methods can damage healthy tissues as well as abnormal cells. They also tend to have debilitating side effects, such as nausea, vomiting, tiredness and hair loss.

Immunotherapy uses the body’s immune system to combat diseases with precision and minimal harm by blocking molecules – called checkpoint inhibitors – like PD-L1 or CTLA-4 that cancer cells use to turn off the immune systems.

Checkpoint inhibitors are a Nobel prize-winning discovery and they’re now one of the most widely used forms of immunotherapy. They work by blocking surface proteins that prevent immune cells from attacking cancer cells. By lifting the brakes on the immune response, these inhibitors unleash the body’s natural defence mechanism against cancer.

Hot and cold tumours

Tumours are often categorised as “hot” or “cold” based on their interaction with the immune system.

Hot tumours are characterised by a robust immune response, with infiltrating immune cells actively engaging with cancer cells. In contrast, cold tumours exhibit minimal immune activity, often evading detection by the immune system.

Immunotherapy has worked in hot tumours such as melanoma, kidney cancer and lung cancers. However, many tumours – such as most types of colon cancer – respond poorly to immunotherapy because they’re able to evade immune surveillance.

However, immunotherapies are emerging that could expand the benefits to more cancer patients, including those with cold tumours. These approaches include combination therapies using more effective immune checkpoint inhibitors with other agents, including chemotherapy and drugs in trials, to prime the immune system and enhance tumour recognition.

There are other approaches too.

CAR-T cell therapy

CAR-T cell therapy involves extracting a patient’s immune cells and genetically engineering them to produce chimeric antigen receptors – proteins on the surface of the immune cells that recognise cancer – before reintroducing them into the bloodstream. Once inside the body, the modified immune cells target and destroy cancer cells. This treatment has been used in tumour conditions like lymphomas or leukaemias but now these are moving into other cancer types.

Invariant natural killer cells

A 2024 trial used “invariant natural killer cells”, which help coordinate the body’s immune response, as immunotherapy during very severe infections, when people affected by a viral attack on their lungs could no longer breathe. The trial found that most patients recovered despite being critically unwell.

Unlike traditional vaccines that prevent infectious diseases, cancer vaccines stimulate the immune system to recognise and attack cancer cells. Cancer vaccines may contain tumour-specific markers called antigens or genetic material to train the immune system to target cancerous cells.

This means that immunotherapy can offer truly personalised medicine. There’s data, for example, on cancer vaccines from clinical trials based on the changes or mutations of a specific patient’s tumour.

Benefits beyond cancer treatment

While immunotherapy has gained widespread recognition for its efficacy in cancer treatment, its applications could extend far beyond oncology. By harnessing the immune system’s ability to distinguish self from non-self, immunotherapy offers promising avenues for combating a diverse range of ailments.

For example, researchers are exploring its potential in treating autoimmune diseases, allergic disorders, infectious diseases, and even neurological conditions like Alzheimer’s disease.

The treatment can be highly effective but it’s not everyone. For reasons we don’t yet fully understand, some people are resistant to treatment. Immunotherapy isn’t free of side effects either. Autoimmune complications can include colon and lung tissue inflammation. The current high cost of immunotherapy can prove prohibitive for many potential patients. Additionally, uptake of the treatment is limited by patient selection – choosing who would most benefit from this treatment and developing personalised treatment regimens remain critical for maximising results.

Ongoing research into immunotherapy could herald an era of targeted and tailored treatments. These include oncolytic viruses that can attack cancer directly, and microbiome modulation, which uses bacteria to enhance the activity of checkpoint inhibitors.

As our understanding of immunology continues to deepen and technology advances, immunotherapy could offer precision medicine and personalised treatments for a host of previously incurable conditions – the challenge is to make it available and accessible to more patients. Läs mer…

A personalised mRNA vaccine to treat melanoma has now reached late-stage trials in the UK. This is just the latest step in improving the cure rate of cancer.

This form of cancer therapy harnesses the power of the body’s immune system to target and eradicate cancer cells. During the phase 2 trials, the vaccine was shown to reduce the risk of cancer returning in people who were undergoing treatment for melanoma.

The phase 3 trials the vaccine is currently entering will recruit thousands of participants in order to better understand just how effective personalised mRNA vaccines are in treating melanoma.

Melanoma, the deadliest form of skin cancer, has been a formidable challenge for doctors due to its aggressive nature and tendency to spread. It’s usually caused by exposure to ultraviolet light – but in many cases we don’t fully understand why it occurs.

Early melanomas can be cut out surgically. But if the cancer is more advanced, or if it has spread to the lymph nodes or other places in the body, patients will need drug treatment too.

We’ve made massive improvements in treating melanoma, especially with drugs that enable the immune system to recognise melanoma cells and kill them (known as immunotherapy). But despite the tremendous successes here, sometimes these drugs are very toxic – causing inflammation of lung or gut tissue, for example. Other times, they fail to work, so melanomas return or spread – known as relapse.

Enter personalised messenger RNA (mRNA) vaccines – a cutting-edge therapeutic approach that leverages the body’s own immune system to fight cancer, potentially with fewer side-effects than existing treatments.

Personalised vaccines

An mRNA vaccine works by introducing fragments of mRNA (messenger RNA) into the body. The main function of mRNA is to copy and carry genetic information from our DNA to other cells.

In the case of a cancer vaccine, these mRNA fragments introduce tumour-specific antigens – abnormal parts of cancer – into the body. These antigens are unique to cancer cells and serve as targets for the immune system to recognise and attack. This means that once the immune cells are primed, if any melanoma cells begin to form in future they’ll know to attack and destroy them. The immune system will also kill any residual microscopic melanoma cells that could be lurking inside patients.

One of the keys to the effectiveness of personalised mRNA vaccines lies in their customisation to each patient’s unique genetic makeup and tumour profile. By sequencing a patient’s tumour DNA, researchers can identify the specific mutations and antigens present in their cancer cells. This information is then used to design a personalised mRNA vaccine tailored to target the patient’s specific tumour antigens.

Melanoma is usually caused by UV exposure.
Nasekomoe/ Shutterstock

The patient’s mRNA sequences are then enclosed in lipid (fat) nanoparticles which act like miniature cargo carriers to deliver the the mRNA into the patient’s body via an injection. Once inside the body, the mRNA molecules instruct the cells to produce the tumor antigens, triggering an immune response that spreads throughout the body. This immune response targets and eliminates cancer cells bearing those antigens.

The immune system plays a pivotal role in cancer surveillance and elimination. This is why mRNA vaccines are increasingly being investigated as a form of cancer treatment, as they train the immune system to recognise and mount a targeted response against cancer cells bearing specific antigens, effectively enhancing the body’s ability to identify and destroy them.

But cancer cells have many techniques they use to avoid detection, allowing them to grow and spread. As such, we don’t currently know whether mRNA vaccines will work alone, or work best in conjunction with existing cancer therapies – and whether vaccines should be deployed as an early or late line of defence against cancer.

At present, the melanoma mRNA vaccine appears to work best when used alongside other cancer treatments. The initial results of the phase 2 trials showed patients who used the personalised mRNA vaccine alongside the immunotherapy drug pembrolizumab had a 49% lower risk of death or melanoma recurrence three years later compared to those who only took the immunotherapy drug.

The phase 3 trials will build on this work, investigating the vaccine in a larger group of people. Hopefully the study will confirm the phase 2 findings and the drug will become available to melanoma patients in the future.

A personalised mRNA vaccine for melanoma would offer a new avenue for treatment – which may increase quality of life and the cure rate of this type of cancer. Vaccines are also being studied for other cancer types, including lung cancer. Research has also shown personalised mRNA vaccines may be effective for treating pancreatic cancer – but again we need more information from larger studies.

Personalised mRNA vaccines represent a paradigm shift in cancer therapy – offering a highly targeted and adaptable approach to treatment. By harnessing the body’s immune system to selectively target cancer cells, these vaccines hold enormous potential to improve outcomes and quality of life for patients. Läs mer…