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Fighting cancer with made-to-measure vaccines

Measurement of T cell responses induced by actively personalised vaccination will provide valuable information. Image courtesy of Immatics
Measurement of T cell responses induced by actively personalised vaccination will provide valuable information. Image courtesy of Immatics

A new wave of personalised vaccines could harness the power of patients’ own immune systems to fight an aggressive form of brain cancer.

Measles, mumps, polio, the flu; think of vaccination today and you probably imagine a healthy person being given a vaccine to protect them from catching an infectious disease. But in the future, the focus is likely to shift towards ‘therapeutic vaccination’, which involves administering vaccines to people in the early stages of a long-term illness in an effort to prevent or reverse its progression.

The targets for new vaccines could be chronic conditions such as Alzheimer’s disease and cancer, or viral infections like HIV or dengue fever.

This trend has been accelerated by advances in genetics and a burst of activity in the field of personalised medicine, and scientists in the EU-funded GAPVAC project say that pulling all of this together presents a new opportunity to change the face of cancer care.

The 15-member consortium of biotech companies and academics has come together to test whether patients with glioma, a form of brain cancer, could be treated with new tailor-made cancer vaccines.

The idea driving GAPVAC is that patients diagnosed with Glioblastoma, a rare form of glioma, could have a vaccine created for them – from scratch – that would be designed to recruit the patient’s immune system in the battle against the cancer.

This personalised vaccine would be tailored to suit both the immune system of the patient, and the specific characteristics of the cancer tumour, said Dr Harpreet Singh, Coordinator of GAPVAC and Chief Scientific Officer of Immatics, a biotech spin-off from the University of Tübingen, Germany.

‘Our goal is to have a specific vaccine for each and every individual patient. This is what we believe is truly personalised healthcare.’

Dr Harpreet Singh, Coordinator of GAPVAC and Chief Scientific Officer at Immatics

‘For patients with glioma, current chemotherapies really don’t work at all. They stop tumour growth but do not significantly improve survival. We believe cancer immunotherapy can change this. The immune system can be very powerful. What we do is activate the immune system to fight against cancer,’ he said.

As part of the four-year GAPVAC project, 30 patients will be enrolled in a clinical trial in 2014 to test the consortium’s system for creating customised vaccines for people with brain cancer.

Finding the differences

There are two steps in the process, which begins when a piece of a glioma tumour from the brains of participating patients is analysed by GAPVAC. First, the researchers select 10 proteins that prompt an immune response –  known as peptide antigens – from a vast warehouse, choosing the ones that are most suited to the patient.

Next, the patient’s genome and the genome of the tumour can be sequenced and compared to find differences between the two. The scientists identify mutations contained in the tumour genome, which allows them to synthetically create tumour-specific peptide antigens. 

Dr Harpreet Singh, Coordinator of GAPVAC and Chief Scientific Officer at Immatics. Image courtesy of ImmaticsDr Harpreet Singh, Coordinator of GAPVAC and Chief Scientific Officer at Immatics. Image courtesy of Immatics

‘The combination of the warehouse approach and the mutation approach would be the ultimate type of tailored therapy,’ Dr Singh said.

There are several reasons for focusing on glioma. For a start, it is a rare disease for which there are very few therapies, meaning the prognosis is grim for patients with this kind of cancer. Through its research funding programmes, the EU is keen to increase its focus on rare disorders, in addition to the research already being carried out into conditions affecting larger numbers.

In addition, a series of recent publications have observed that brain cancer antigens make particularly good targets for therapeutic vaccines.

GAPVAC hopes the study, which will be finalised in 2017, will demonstrate that the method is feasible in the real world and safe for the patients taking part in the trial. The next step would be to test whether it increases survival rates in a large number of patients, and to compare the vaccine with currently available chemotherapies. Similar vaccine therapy research is also being undertaken by two other EU-funded projects: HEPAVAC, which looks at treating the most common form of liver cancer, hepatocellular carcinoma, and IMPROVE, which focuses on improving prostate cancer outcomes through vaccines.

The approach taken by GAPVAC would, according to Dr Singh, represent the ultimate achievement of personalised medicine. ‘Our goal is to have a specific vaccine for each and every individual patient. This is what we believe is truly personalised healthcare.’

If successful, the project would not only improve the prospects for brain cancer patients, but offer hope of a new approach to treating other cancers too.

The first vaccines

Vaccines research has come a long way since 1796 when Edward Jenner, an English doctor, inoculated an eight-year-old boy named James Philips with pus taken from a cowpox sore on the hand of Sarah Nelmes, a local milkmaid. (The word ‘vaccine’ comes from ‘vacca’, the Latin word for cow.)

Jenner had observed that milkmaids were less likely than average to contract smallpox and believed their exposure to cowpox was making them immune. He showed that James Philips could be protected from smallpox infection, by switching his immune system on using cowpox pus. Thus began a field of research that has saved countless lives all over the world.

Fast-forward almost 200 years and, in 1979, the World Health Organisation declared smallpox to be the first infectious disease to be eradicated. Childhood immunisation programmes have made cholera, diphtheria, whooping cough, and polio – amongst others – a rare sight in the developed world. Death rates from infectious diseases like pneumonia and measles have plummeted in poorer countries too. 

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