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I’ve been asked a few times recently whether the speedy development of COVID-19 vaccines means anything for cancer treatment – so a thread
with a few thoughts - would love to hear yours!
with a few thoughts - would love to hear yours!
First, a bit of background on immunotherapies in cancer...
In cancer development our immune system fails to notice when our cells go faulty – the core basis of cancer immunotherapy is to prime the immune system to recognise molecular red flags to re-start this process [2/17]
In cancer development our immune system fails to notice when our cells go faulty – the core basis of cancer immunotherapy is to prime the immune system to recognise molecular red flags to re-start this process [2/17]
These could be via immune proteins (antibodies), engineered immune cells, viruses designed to attack cancer cells & vaccine-like technologies
But, guess what, it turns out to be quite complex (twas ever thus with cancer!) [3/17]
But, guess what, it turns out to be quite complex (twas ever thus with cancer!) [3/17]
Viruses are foreign invaders, so it’s easy for the immune system to spot molecular hallmarks (‘antigens’) as different – vaccines are designed to show these antigens to the immune system so it can build a long-lasting defence without actually getting the disease [4/17]
![Viruses are foreign invaders, so it’s easy for the immune system to spot molecular hallmarks (‘antigens’) as different – vaccines are designed to show these antigens to the immune system so it can build a long-lasting defence without actually getting the disease [4/17]](https://pbs.twimg.com/media/EycJQhCXEAIKT0l.png "Viruses are foreign invaders, so it’s easy for the immune system to spot molecular hallmarks (‘antigens’) as different – vaccines are designed to show these antigens to the immune system so it can build a long-lasting defence without actually getting the disease [4/17]")
For COVID-19, scientists quickly settled on what the key antigen was, namely the Spike protein. For cancer vaccines (treating, rather than preventing), the first problem is knowing which antigens to use to soup up the immune system [5/17]
Some antigens are normal cellular proteins that are amplified in tumours – but immune cells are used to seeing these and they’re also present on normal cells, so it’s hard to kick-start an immune reaction and it can attack lots of healthy tissues [6/17]
Other antigens result from mutations (‘neoantigens’) – these look different
& found only on tumour cellsbut may differ from patient to patient
, be expensive & slow to manufacture tailored therapies, & difficult to pick up in cancers with few mutations[7/17]
& found only on tumour cellsbut may differ from patient to patient, be expensive & slow to manufacture tailored therapies, & difficult to pick up in cancers with few mutations[7/17]
So there are a lot of large-scale efforts (with clever people and whizzy computers) to identify neoantigens and work out how to use these to trigger an appropriate immune response [8/17]
And the immune response is REALLY complicated.
There are myriad immune cells performing myriad functions – patrolling, presenting antigens, regulating other cells, churning out antibodies, forming 'memory' – all with the right chorus of stimulating and suppressing signals [9/17]
There are myriad immune cells performing myriad functions – patrolling, presenting antigens, regulating other cells, churning out antibodies, forming 'memory' – all with the right chorus of stimulating and suppressing signals [9/17]
One of the biggest breakthroughs in cancer immunotherapy (after much disappointment) was the discovery of signals cancer cells tune up that put a dampener on the immune response – ‘immune checkpoints’
By blocking these blockers, it could re-awaken an anti-tumour effect [10/17]
![One of the biggest breakthroughs in cancer immunotherapy (after much disappointment) was the discovery of signals cancer cells tune up that put a dampener on the immune response – ‘immune checkpoints’ By blocking these blockers, it could re-awaken an anti-tumour effect [10/17]](https://pbs.twimg.com/media/EycJRTsWYAEMS9g.jpg "One of the biggest breakthroughs in cancer immunotherapy (after much disappointment) was the discovery of signals cancer cells tune up that put a dampener on the immune response – ‘immune checkpoints’ By blocking these blockers, it could re-awaken an anti-tumour effect [10/17]")
By blocking these blockers, it could re-awaken an anti-tumour effect [10/17]
But they don’t work for every patient (and it’s hard to predict upfront), some tumours develop resistance (and this is hard to predict), and some patients suffer really nasty side effects (yep, also hard to predict) [11/17]
So COVID-19 vaccines are different to therapeutic cancer vaccines (or immunotherapies in general), but the past year does remind us of a few things that are relevant... [12/17]
Invest in the science! It needs an army of scientists steeped in this complexity to figure out the right antigens, how to target safely & effectively, predict side effects – & mRNA tech was based on years of basic RNA cancer vaccine research [13/17]
The vaccines were developed in rapid time but they were built on long-built foundations of knowledge of intricate biology
And look! This is critical, as the CD25 story shows [14/17] https://www.ucl.ac.uk/cancer/news/2020/nov/interview-developing-new-immunotherapy-gain-control-cancer
And look! This is critical, as the CD25 story shows [14/17] https://www.ucl.ac.uk/cancer/news/2020/nov/interview-developing-new-immunotherapy-gain-control-cancer
Invest in the infrastructure! It often requires the manipulation and production of biotherapies – viral vectors, RNA or DNA molecules, engineered immune cells – and this is costly and complicated. Infrastructure isn’t sexy, but it’s crucial [15/17]
Get the right people together! COVID-19 vaccines have been a truly team effort – scientists, clinicians, technologists – all bringing vital knowledge and expertise and rapidly sharing data. Plus the right industry partners to get these to the clinic at pace and scale [16/17]
If we can keep that spirit and momentum going, then it’s really exciting to think about what progress we can make in cancer over the next few years – but we need sustained investment alongside the ambition, and to recognise and reward collaborative research [17/17]
