In October Cancer Research UK (CRUK) launched the Cancer Research UK Grand Challenge – a £100m scheme to tackle seven of the biggest challenges in understanding and treating cancer.
And in a series of posts over the next two months they will be exploring each of the seven Grand Challenge questions set by a panel of the world’s leading cancer experts, starting with question one: Can we develop vaccines to prevent cancers that aren’t caused by viruses?
Many of us will be familiar with the idea of vaccines – one of the greatest advances in medicine – which trigger our immune systems to recognize and attack infectious diseases. Vaccines remain the only medical advance to have ever fully eradicated a disease, ridding the world of the smallpox virus.
But the big question is: could a vaccine do the same for cancer? Obviously, cancers aren’t infections – unlike bacteria and viruses, they develop from our own cells, posing a big challenge for our immune system in recognizing them as harmful.
Nevertheless, harnessing the power of the immune system to fight cancer has been a goal for scientists for over a century. But it’s only recently that we’ve begun to understand exactly how immune cells (mistakenly) view cancer as a friend to leave in peace, rather than an enemy to destroy. And then harness this knowledge to develop new cancer treatments.
But this has also raised the question of whether we might be able to use vaccines to prevent – as well as treat – the disease.
Vaccines work by training the immune system to recognize small, harmless pieces of a disease, so that it can eradicate anything that looks like it in the future. Once convinced that a particular molecule belongs to the enemy, the immune system is forever primed to treat it as hostile.
Vaccines have already been developed against certain forms of cancer that are caused by viruses, such the human papillomavirus (HPV) – which causes cervical, oral and anal cancers. And eradicating cancers caused by the Epstein Barr Virus (EBV) – such as certain forms of lymphoma – is the second of our Grand Challenge questions (more on this to come in the next of the series). So the idea of creating a vaccine to prevent or treat cancers linked to viruses certainly works in theory.
But only three in every 100 cancers in the UK each year are linked to infections. And in these cases the immune system’s target is distinct – it’s definitely ‘foreign’.
Without that ‘foreign invader’, alerting the immune system becomes a lot more complicated.
So the first challenge set by our panel is to take this a step further, and find a way to directly target cells in our bodies in the earliest stages of becoming a cancer. Helping the immune system destroy these abnormal cells before they develop into cancer could not only save lives, but spare thousands from even becoming a cancer patient in the first place.
It sounds incredible – so how might this work in practice?
What do we mean by a cancer jab?
Professor Tyler Jacks, director of the Koch Institute for integrative cancer research at MIT in the US, and one of the members of our Grand Challenge scientific panel, redibly excited by the prospect of this question.
“To be clear, the point is not to have a one-size-fits-all vaccine preventing all cancers,” he explains.
“Every cancer is different. But I would be happy, I would be thrilled actually, if this question stimulated research that found a set of molecules, probably not just one, which we could develop into a vaccine for people at a higher risk of certain cancers.”
Professor Christian Ottensmeier, a Cancer Research UK expert in immunology at the University of Southampton, shares his enthusiasm. “It’s entirely possible that as a result of this Grand Challenge people will start to look at the puzzle of preventative vaccination in a different way,” he says.
“So I’m really excited about this opportunity, because I think this will make the research community look at this particular question in a way it hasn’t so far.”
But creating a vaccine to prevent cancer is easier said than done, and Professor Jacks sees several important steps that must be overcome, each with its own unique challenges and hurdles. But the biggest, he says, is the first – finding targets for the vaccine that are hallmarks of developing cancer cells.
Spotting cancer before it happens
Finding suitable vaccine targets requires researchers to pinpoint molecules that the immune system can recognize as ‘foreign’. These are known as ‘antigens’.
“We know that cancers develop due to changes in the DNA,” says Jacks. “Some of these genetic mistakes will result in molecules that look completely different to how they should in a normal healthy cell. If we can find which of these mutations are common in certain types of cancer, we might be able to use these in a vaccine against that cancer type.”
Alongside these faulty ‘self’ molecules, researchers have also found that certain forms of cancer produce normal molecules when they shouldn’t, or in far greater amounts than healthy cells. These are known as ‘tumour-associated antigens’. For example, a molecule that’s only made during early childhood and not at all in a healthy adult might be switched back on and produced inside cancer cells to help them grow.
And as well as these faulty or inappropriately produced molecules, there could be an entirely new method for finding the best targets.
According to Ottensmeier it’s difficult to know what the explosion in data generation will lead to.
“Even three to five years ago it was unimaginable that you would even consider making a patient -specific vaccine,” he says.
“But now that’s already a reality with a number of bespoke, experimental ‘vaccines’ in development as treatments.”
Finding the target is just the first step
Once a suitable collection of vaccine targets are found, there would then be a huge amount of work to make sure the vaccine actually worked, and was safe.
Neither of these will be easy. And since the goal is to create something that protects over a lifetime, it won’t be quick either. It could take decades to ensure that a vaccine preventing cancer in the general population truly works.
But rather than going for this ultimate goal, Ottensmeier thinks that a better strategy – and one that might be achievable within the timeframe of our Grand Challenge – could be to identify and begin developing vaccines that could be used among small groups of high risk patients – for example, women with a family history of breast cancer.
“Women with known faults in their DNA are already offered preventative measures,” he says.
For some this may involve a double mastectomy, like the high-profile actress and filmmaker, Angelina Jolie had in 2013.
“But what if we could offer these women a vaccine against breast cancer rather than surgery?” asks Ottensmeier. It’s a tantalising prospect.
The patient perspective
The Grand Challenge that most excites me has to be research into a vaccine to help prevent cancer. Easy words to write – but I’ve probably only a small idea of what a huge undertaking this is. When I was diagnosed with lung cancer with a prognosis of three months, I was left wishing I could pop along to my GPs for a cancer jab and it would all be over (we didn’t even have the flu jab then). But that wasn’t to be, and it’s a small miracle that I am still here. Reading through the seven questions put forward I was unsure which one I would like to see a group of scientists take on. But as I looked up from my laptop, stuck on the rim of a shelf, was a yellow sticky note reminding me that I was due for my flu jab that afternoon. Believe me, my selection is not one of divine intervention, rather the simplicity of its use if it was to work.
– Terry, patient panel member for the Grand Challenge
A Grand Challenge should be challenging, and shouldn’t be obvious. It’s up to the applicants to come up with the best way to tackle this problem, but the rewards could be incredible if successful.
Director of the Koch Institute for integrative cancer research at MIT
Our understanding of the immune system has come on in leaps and bounds in the last decade, and the resulting progress in immune-based treatments has made things possible that were previously considered completely untenable.
So, in a period of such rapid progress, Professor Jacks argues: “Why not reach for the stars a little bit here”.
“A Grand Challenge should be challenging, and shouldn’t be obvious. It’s up to the applicants to come up with the best way to tackle this problem, but the rewards could be incredible if successful.”
And being on the cusp of discovery is exactly how this type of research should be carried out. “Honestly, we just don’t know if we can do this,” he says.
“But failure in research is commonplace. We make progress despite a great deal of failure.
“If you don’t try, you’ll never succeed, and just because it might not work is no reason not to try.”
If you’re a researcher and want to build a team to take on this challenge, visit CRUK’s website to find out how you can apply.