What's new in cancer?: Vaccines
What single innovation do you think has made the biggest contribution to global health? It’s a tough question. Sanitation? Antibiotics? A strong contender for the title would be vaccination.
Vaccination and immunotherapy as a treatment
The ability to stimulate our immune systems to seek and destroy disease causing organisms has prevented the death of millions of people globally. Starting with Edward Jenner’s experiments with cowpox in 1790’s through to successes with MMR, whooping cough, TB and now covid-19, preventive vaccination has been a mammoth success story.
Preventative vaccines not only stop infections, but they also stop cancer. The highly infectious human papilloma virus (HPV) causes genital warts. The HPV types 16 and 18 were very common and can lead to cervix cancer as well as tonsil and anal cancers. A HPV vaccine program has meant that the presence of HPV 16 and 18 in sexually active 16-18 year old females has reduced from over 15% prior to vaccination to 0% in 2018 (10 years after vaccination introduced). This is a major triumph in cancer prevention.
Given the successes in disease prevention it is not surprising that researchers might want to use vaccination and the immune system as a treatment.
The best documented first attempt was by Dr William Coley, an American bone surgeon. Coley noted that bone cancer (sarcoma) sometimes reduced in patients with infection. Based on this observation he injected patients with a cocktail of infections known as ‘Coley’s Toxin’. In 1891 he reported some benefits, but he was not widely believed. The reasons for these responses are now better understood and Coley has been called ’the Father of Cancer immunotherapy’. Using a similar principle it was identified that the bacillus camette-guerin (BCG) could treat bladder cancer and this treatment is still used today when it is instilled in the bladder.
The last decade has brought incredible success with immunotherapy. Antibodies which ‘unmask’ cancer and allow our immune system to ‘see’ it have brought some of the most exciting cancer advances of the last decade. The clear benefits of these drugs have galvanised more and more immune system research in cancer.Last year there were nearly 6000 trials running using these drugs and many of them are already in established use across the UK.
Cancer vaccine research and mRNA technology
There have been multiple attempts to develop vaccines for cancers but disappointingly most have not delivered on their promise. After many negative trials it seemed to some that cancer vaccines were never going to prove to be useful, but things have changed.
A significant problem for a cancer vaccine is to find something that uniquely represents the cancer for the immune system to target (an antigen). No two cancers are exactly genetically alike, meaning that there is no clear immune target for a vaccine. Using genetic code from the tumour had previously been attempted with DNA but this could sometimes be incorporated incorrectly into the patient’s own genetic code. The development of messenger RNA (mRNA) technology allows a laboratory to take a few key genetic signatures from a tumour and build this into a tailored vaccine.
Getting the RNA into the immune system is also challenging but embedding them into nanoparticles seems effective and prevents the RNA being destroyed by the immune system before they have triggered a response.
Some important trials were launched in 2019. mRNA technology then took centre stage in 2020 when the same technology was used to develop covid vaccines – finding the genetic code that identified the distinctive spike protein in the virus. Whilst the massive switchover to covid from cancer greatly slowed the cancer trials, the lessons learnt in vaccine production were so valuable that ultimately most would conclude that it has benefitted cancer vaccine development.
Promising trials
The last few months have seen results from two trials which have justified excitement in the vaccine approach. In April the American Association for Cancer Research meeting heard how a mRNA vaccine showed superior efficacy to standard immunotherapy in high-risk melanoma treatment. In May 2023 Nature reported on the first phase of a study in pancreas cancer. Surgeons in New York shipped pancreas tumour fragments to Germany where, in 72 hours, those tumours were genetically sequenced, and a customised vaccine manufactured. These vaccines stimulated an immune response in recipients similar to that seen in long term survivors of pancreas cancer. The results are promising enough to lead to a much larger trial.Not only have these results prompted more research they have led to the UK Government to partner with BioNTech to deliver cancer vaccines in the UK. BioNTech said they were attracted to the offer because of the UK’s genetics research and track record of covid vaccine rollout.
It feels disappointing, but important to discuss the topic of anti-vaxxers. The topic is as old as vaccination itself. Gilray’s famous 1802 cartoon of small cows erupting from cow-pox vaccinated people was published soon after Edward Jenner’s famous paper outlining the benefits of the inoculation. ‘Anti-vacks’ (as Jenner called them) really started organising themselves when vaccination became compulsory by state act in 1853. Mandatory vaccination was seen as an assault on liberty. One tactic used was to discredit the vaccination by casting doubt on both efficacy and safety. These techniques hadn’t changed 170 years later when they were used by covid anti-vaxxers. We might hope that cancer treatment benefits (which will not be mandatory) will avoid anti-vaxx scepticism and safety testing will be intense.
Looking to the future
These technologies are some way from routine clinical use but both the melanoma and pancreas trial were able to report results in just a few years. The new speed of development brought by covid experience and now big cash investment should help us prove vaccine benefits in years rather than decades and, to borrow from Edward Jenner “to inspire the pleasing hope of its becoming essentially beneficial to mankind”.
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