Research raises hope of a 'Holy Grail' universal cancer vaccine

3 June 2016

Breast cancer screening

''Universal cancer vaccine' breakthrough claimed by experts,' The Independent reports.

Researchers extracted genetic code called RNA from cancer cells, embedded them in nanoparticles to make them appear like viruses or bacteria, and injected them into mice to 'teach' immune cells to attack cancer cells.

In most cancer cases, the immune system ignores cancer cells as it cannot tell the difference between these and healthy cells. This makes it vital to give the immune system the ability to recognise and target cancer cells.

Researchers developed the vaccine after a series of experiments on mice, using different types of RNA-containing nanoparticles (tiny particles that can be as small as a billionth of a metre) disguised in fatty acid (lipid) coatings. They discovered the type that worked best to reach the relevant parts of the immune system.

After showing that the vaccines worked on mice with artificially induced tumours, the researchers began early human trials.

They used a low dose of the vaccine in three people with malignant melanoma, a type of skin cancer.

All three responded by producing T cells to target the cancer cells, in the same way as if their body had detected a virus or bacteria. Side effects were reported to be brief flu-like symptoms.

We now need to see the results of larger trials in many people with different types of cancer to assess whether a 'universal' cancer vaccine could be made based on these techniques.

Where did the story come from?

The study was carried out by researchers from Johannes Gutenberg University, Biopharmaceutical New Technologies, Heidelberg University Hospital and the Cluster for Individualized Immune Intervention, all in Germany.

It was funded by the technology innovation programme of the Rhineland Palatinate government, the InnoTop programme, the CI3 Cutting Edge Cluster Funding of the German Ministry of Technology (BMBF), and the Collaborative Research Group 1066 of Deutsche Forschungsgemeinschaft.

The study was published in the peer-reviewed journal Nature.

Most of the UK media covered the story responsibly and accurately, making it clear that these are very early-stage trials and much work remains to be done. The Guardian and the Daily Mail did a good job of explaining the science.

What kind of research was this?

The study in humans was a phase 1 trial, which is aimed at checking the safety and initial effects of the vaccine.

It followed a series of studies in mice, where researchers tested which type of nanoparticle was best taken up by the relevant cells of the body.

They then investigated the effects of nanoparticles containing cancer RNA, both as a protective vaccine and then in mice that had already been given cancer.

This combination of animal studies and very small-scale studies in humans is typical of the early stages of drug or vaccine development. These studies help researchers work out whether a treatment is worth testing in proper clinical trials.

What did the research involve?

Researchers began with a series of tests on mice to identify types of nanoparticle that can deliver a fragment of RNA to dendritic cells, which flag up viruses and bacteria to the immune system.

They did this using RNA that causes cells to emit light (fluoresce), so they could see where in the mice's bodies the particles ended up. They then tested nanoparticles containing cancer RNA on a series of genetically engineered mice to see what effect they had.

Finally, the researchers injected three people who had malignant melanoma with small doses of nanoparticles containing RNA that encodes four proteins usually produced by malignant melanoma cancer. They measured the immune response mounted by the patients' bodies.

The first part of the research showed that adjusting the proportions of fatty acids to RNA in the nanoparticles affected their electrical charge, which allowed them to be directed to the areas of the body where dendritic cells are most common, such as the spleen.

The following experiments used RNA from mouse cancers in the nanoparticles. The researchers wanted to see whether giving mice a vaccine before injecting them with cancer cells would prevent the growth of tumours.

They then looked at the effects of giving the mice a vaccine several weeks after they had been injected with cancer cells. They compared vaccinated mice with non-vaccinated mice.

They also looked at the effects of the vaccine on mice genetically engineered without certain working parts of the immune system to see which parts of the immune system were important for the vaccine to work.

Finally, the researchers recruited three skin cancer patients with advanced disease and gave them first a very low dose, then four weekly doses at a higher level (but still proportionately lower than that given to the mice) of the RNA nanoparticles.

They monitored the patients for side effects and tested their blood for antibodies to the cancer, as well as for signs of production of the immune system signalling protein, interferon alpha, and T-cells. 

What were the basic results?

In the mouse studies, all mice given the vaccine before being injected with cancer cells remained cancer-free, while all untreated mice died within 30 days.

Mice vaccinated after being given cancer cleared the tumours within 20 days of vaccination, while untreated mice continued to grow tumours.

The three people treated with vaccine all released alpha-interferon in response to the vaccine and produced T-cells against the antigens in the vaccine.

They all had a short flu-like illness after vaccination – similar to the reaction you get when your body is fighting off a virus.

The study was not designed to find out whether the vaccine cured the cancer. However, the researchers say that in one patient, scans before and after the vaccine showed a tumour had shrunk.

One patient who had their tumours removed surgically before vaccination remained tumour-free seven months later.

The third, who had eight tumours that had spread to their lungs, had no growth in those tumours, although the researchers do not say what the time period was for this. 

How did the researchers interpret the results?

The researchers say that this type of vaccine is 'fast and inexpensive to produce' and 'virtually any tumour antigen can be encoded by RNA' – meaning that this type of vaccine could be potentially used against any type of cancer.

Their approach 'may be regarded as a universally applicable novel vaccine class for cancer immunotherapy', they say.

Conclusion

It's important to keep a sense of proportion when researchers make sweeping claims, such as stating that they have developed a vaccine that can work against all cancers.

While the scientific advances are important and could lead to future treatments, we don't yet know whether this approach is safe, effective or practical in humans.

Early studies like this create an enormous amount of interest. But studies in animals often don't work out so well when they're carried out in humans.

And dose-escalation studies are primarily done to make sure the treatment in question doesn't have obvious, catastrophic effects – they aren't designed to show whether the treatment actually works.

In a comment on the study, also published in Nature, experts say the new approach 'may give a strong boost' to the cancer vaccine field, and that 'the results of forthcoming clinical studies will be of great interest'.

The key point is that we need to wait for the results of those studies. Early results in three patients, all with the same type of cancer, do not tell us whether researchers have indeed hit on the 'Holy Grail' of a universal cancer vaccine.

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