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Immunotherapy: puzzles and promise

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by Cancer Research UK | Philanthropy and partnerships

25 January 2024

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Lung cancer cell
Lung cancer cell Credit: LRI EM Unit

Our mission is to beat cancer. Thanks to our generous supporters, we’re able to fund the best research to help us do that. Immunotherapy is one of today’s medical hot topics, but what is it, and why are we so excited about it?


Immunotherapy works by harnessing the power of our own immune system to attack and kill cancer cells – something it normally does, but that cancer can interfere with. It’s also a promising alternative to less targeted options like chemotherapy that we’ve become familiar with.

How did this deceptively simple-sounding idea of using our own cells to treat cancer come about?

 

Rudolf Virchow
Rudolf Virchow Wellcome Collection Copyright: Attribution 4.0

The beginnings

In the 1860s, physician Rudolf Virchow declared, “Most diseases of mankind can be understood in terms of the dysfunction of cells”. Cancer is definitely a disease of cells – our own cells going rogue, multiplying when they shouldn’t, changing their surroundings and using our biological systems to grow and spread.

Virchow also noticed that immune cells “decorate” cancers. That is, tumours aren’t just a mass of cancerous cells – our body’s defences could be found among them, too.

Then, in the 1890s, the surgeon William Coley first tried to use mixtures of bacteria to make the immune system attack cancer. For this, he’s recognised as the father of immunotherapy, although some problems with infection (perhaps unsurprisingly) arose from his otherwise innovative plan.

William B Coley with Helen Coley Nauts
Image: Cancer immunotherapy pioneer, William Coley, with his daughter Helen Coley Nauts

Coley’s daughter, Helen Coley Nauts, co-founded the New York Cancer Research Institute in 1953 and is credited with resurrecting and shaping cancer immunotherapy as a field. In the same year, the structure of DNA was revealed, and a lot’s happened since then. Transplant medicine advanced and many effective vaccines against disease were made available.

Today, we know more about how our cells work. Thanks to these advances and more, we’re now much better placed to make progress. After more than a century, we finally have the technology to make harnessing the immune system to treat cancer a reality.

The challenges

Despite justifiable optimism, we still have to overcome some big hurdles before immunotherapy starts to show the same benefits we’ve seen from more established treatments like radiotherapy.

First, advances in immunotherapy aren’t helping everyone yet. It’s been transformative for a fortunate minority, so the next step is to make sure immunotherapies work against more cancer types and for more people.

Second, the immune system is powerful and potentially dangerous. Auto-immune diseases like multiple sclerosis, psoriasis and rheumatoid arthritis happen when our immune system doesn’t know when to quit. Overreactions to infections can cause coma or even be fatal. So, if we can boost our immunity to attack tumours, we also need to make sure it doesn’t spiral out of control or last too long.

Third, solid cancers have proven much more difficult to treat with immunotherapy than blood cancers. Tumours can be like walled-off castles, blocking access to our army of immune cells. They can also exhaust immune cells so they can’t make a difference, or the tumour environment can be so full of obstacles blocking their function that they simply can’t do their jobs, even if they’re already inside.

This is where combination treatments come in, which could help overcome barriers to safe and effective immunotherapy. But these can also create more hurdles, particularly in terms of side effects, which can be severe and affect a lot of people.

It’s essential we fund more discovery research that helps us learn exactly what’s going on in different tumour types – and even inside individual tumours – so that personalised immunotherapies tailored to unique tumour environments can reach their potential and wipe cancer out.

Combining immunotherapies together or with other cancer treatments – even ones that haven’t showed very promising results to date – is also a promising strategy. In the 1990s, scientists thought that by cutting off tumour blood vessels using anti-angiogenic drugs, they could starve tumours – like killing a weed root-first. But the drugs’ performance was, unfortunately, disappointing.

Now, clinical trials are finding that anti-angiogenics can ‘normalise’ blood vessels growing into tumours, which can help ICI drugs to awaken immune cells. Immunotherapy combinations like this can even be effective against some late-stage cancers that have already spread, and metastasis remains one of the greatest challenges for cancer treatment.

Here’s a glimpse of the research we’re funding that’s helping to break through barriers to available, successful and safe immunotherapies.

 

Inside the toolbox

There are five main types of immunotherapy at various stages of development today:

  • Cancer vaccines: like vaccinations against infectious diseases but they prime our immune system to destroy cancer.
  • Immune checkpoint inhibitors (ICIs): these Nobel prize-winning drugs release the brakes on our immune cells so they can get to work attacking cancer.
  • Adoptive cell transfer: immune cells are taken from a person with cancer, retrained and multiplied in the lab, then reintroduced to the body. CAR-T-cell therapy is the best-known example.
  • Cytokine therapies: small drugs that modify cell-to-cell chatter in the body to encourage immune responses to cancer.
  • Oncolytic (cancer-killing) viruses: viruses engineered by scientists in the lab to be safe for people overall, infecting and killing only cancer cells.

 

At a glance: our immunotherapy innovators

Understanding and predicting cancer’s trajectory

Professor Samra Turajlic
Professor Samra Turajlic is based at the Francis Crick Institute in London and is a consultant medical oncologist at the Melanoma Unit at the Royal Marsden hospital as well as the leader of our TRACERx Renal study of kidney cancer evolution.

Professor Samra Turajlic is determined to understand why immunotherapy doesn’t work for everyone. She tells us, “Our team recently found clues to why ICI drugs can stop working for some people, through our PEACE (Posthumous Evaluation of Advanced Cancer Environment) study, which allows people with late-stage cancer to donate samples of their tumours both before and after death.

Recently, the team discovered that genetic errors can pile up inside melanoma skin cancer cells that have spread around the body. This in turn can block ICI drugs’ ability to unstick immune cells’ brakes, keeping cancer cells hidden from them.

Learning details like this can be the key to overcoming treatment resistance through better drugs and new combination therapies.

 

Vaccines setting the immune system’s sights on lung cancer

Professor Fiona Blackhall
Professor Fiona Blackhall is chief investigator for the MAGE vaccine trial and professor of thoracic oncology at the University of Manchester. She is also director of research and innovation and a consultant medical oncologist for The Christie NHS Foundation Trust as well as a principal investigator on our TRACERx lung study.

Our Centre for Drug Development is managing and supporting the MAGE vaccine trial, which Professor Fiona Blackhall is leading. The trial is testing the safety of a cancer vaccine treatment for people with advanced non-small cell lung cancer (NSCLC). The first person was treated on the trial in December 2021. “There’s an urgent need to find better treatments for patients with NSCLC,” explains Professor Blackhall, “This is advanced technology targeting a person’s immune system to tackle cancer cells.”

The research team wants to see if it’s possible to ‘prime’ the immune system to attack lung cancer, using vaccines that deliver tiny pieces of tumour cells to immune cells – like presenting a scrap of clothing left by a suspect to a trained dog’s nose. The hope is that the vaccines will make the combination of ICI immunotherapy drugs with chemotherapy even more effective.

NSCLC is the most common type of lung cancer but remains very hard to treat. If successful, this cutting-edge immunotherapy could provide an effective, much-needed new treatment to help more people survive their lung cancer.

- Dr Nigel Blackburn, Director of the Cancer Research UK Centre for Drug Development

Today, fewer than 1 in 5 people with lung cancer live for five or more years after diagnosis in the UK, so when keen gardener and former art teacher Eileen was told she had lung cancer in 2016, she thought, “this is it.” 

But after surgery, radiosurgery, immunotherapy and radiotherapy, her disease is now stable. She received atezolizumab, an ICI drug, in the DARWIN2 trial for TRACERx participants with NSCLC. We run this trial with UCL Cancer Trials Centre and Professor Charles Swanton is the chief investigator.

“Without scientific research it wouldn’t have existed and I wouldn’t be here today.” – Eileen

Along the way, she also signed up to PEACE. Eileen hopes that discoveries made in these studies, which are tracking cancer development in unprecedented detail, will lead to clinical trials and eventually kinder treatments – including immunotherapies that more people can benefit from.

Since launching in 2016, PEACE has grown into a national autopsy programme for people who die with cancer, and participants like Eileen make a vital contribution to research that will go on to save lives.

This is just a snapshot of what we and researchers around the world are doing together to make sure immunotherapy lives up to its potential and saves as many lives as possible. Visionary philanthropic support will help us realise a future of kinder, more effective treatments – with immunotherapy playing a major part.

 

Written by Dr Marianne Baker, Science Engagement Manager at Cancer Research UK.

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