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Clues to why 'vaccine' for prostate cancer works

Monday 16 December 2013

A new vaccine for prostate cancer “could save thousands of lives”, The Daily Telegraph reports.

The paper says that “scientists at Nottingham Trent University believe they have found a vaccine that can effectively ‘switch-off’ cancerous tumours by spurring the immune system into overdrive”.

This news story is based on research in mice designed to learn more about how Provenge – a new vaccine treatment for advanced prostate cancer – works. The vaccine “reprogrammes” the man’s own immune cells to attack the prostate cancer cells. It does this by training the immune cells to recognise a specific protein (PAP) that is found in most prostate tumours, and trigger an immune response to it.

The researchers in the current study wanted to see exactly which areas of the PAP protein prompt the immune response, as this information may help in designing improved vaccines. They identified three parts of the PAP protein that can prompt an immune response. The immune response to one of these sections of the protein prevented tumour growth in the mice. Therefore, the vaccine may have its effect by targeting this part of the protein.

Previous studies comparing the vaccine with an inactive placebo have demonstrated that it improves survival by a few months in a specific group of men with advanced prostate cancer. Earlier this year the European Medicines Agency (EMA), which regulates medicines in Europe, recommended that the vaccine is granted marketing authorisation for men with these specific disease characteristics.

Where did the story come from?

The study was carried out by researchers from Nottingham Trent University and was funded by a programme grant from the John and Lucille van Geest Foundation. The study was published in the peer-reviewed European Journal of Immunology.

The Telegraph story only introduces the fact that the research was in mice towards the end of the article. Stating this earlier on would make it clearer to the readers sooner that this research is at an early stage.

The term "vaccine" may lead readers to wrongly assume this is a vaccine to give protection against getting prostate cancer. However, the vaccine in question is a treatment for advanced prostate cancer – rather than a preventive immunisation. It is called a vaccine because, like preventive vaccines, it works via the immune system.

The term "life-saving" in the media is also perhaps a little optimistic. The studies so far have demonstrated that in men with advanced prostate cancer it prolongs survival by a few months compared with placebo. The vaccine is not "life-saving" in the sense that it is not a cure that completely prevents death from the disease.

What kind of research was this?

This was animal research designed to investigate how a new vaccine for the treatment of advanced prostate cancer (brand name Provenge, chemical name sipuleucel-T) works.

Previous trials have found that Provenge can prolong overall survival in a specific subgroup of men with advanced prostate cancer – those whose cancer had not responded to previous hormone treatment, had spread to bone or soft tissue but not to other bodily organs, and who had few or no symptoms. Treatment options are currently limited for this group of men. The vaccine has already been approved for use in the US and Europe.

The vaccine acts by getting the immune system to recognise and attack prostate cancer cells. The vaccine targets a particular protein called prostatic acid phosphatase (PAP) that is produced at high levels by most prostate cancers. To make the vaccine, doctors collect a certain type of white blood cell from the man’s own blood, and then treat these immune cells with a chemical that allows them to recognise and mount an immune response against PAP when injected back into the man’s bloodstream in the form of the vaccine.

In the current study, the researchers were interested in exactly what precise parts of the PAP protein might be being recognised by the vaccine, and therefore responsible for its ability to improve survival in men with advanced prostate cancer.

As there is a rodent equivalent of the PAP protein, the researchers used mice as a model to see what part of PAP is recognised by immune cells, which immune cells are involved, and how tumour growth is prevented by the immune response.

What did the research involve?

The researchers looked at which parts of the PAP protein were targeted in the immune response in mice. They also looked at which immune system cells in the mice were mounting the response.

They then took the part of the protein that elicited an immune response and developed two different types of the vaccine against it. They then tested whether the vaccines could reduce growth of prostate tumours in mice. The mice either had established prostate tumours or had been injected with tumour cells.

What were the basic results?

The researchers identified three parts of the PAP protein that mice produced an immune response to (called PAP-114-128, 299-313 and 230-244). They focused on studying the PAP-114-128 part of the protein, as it is identical in mice and humans.

The researchers showed that vaccines generating an immune response against PAP-114-128 could slow tumour growth and increase survival in mice with established prostate tumours. It could also slow growth of prostate tumours and increase mouse survival if they were given to unaffected mice that were later injected with prostate tumour cells.

How did the researchers interpret the results?

The researchers conclude that: “PAP-114-128 appears to be a highly relevant [target] on which to base vaccines for the treatment of prostate cancer”.


This animal research has identified a part of the prostate acid phosphatase protein that can be targeted by vaccines to reduce prostate cancer growth. The PAP protein is the target of a new prostate cancer vaccine Provenge (sipuleucel-T) – and the researchers wanted to identify exactly which part of the protein might be targeted by this vaccine.

Previous studies have demonstrated that Provenge can prolong survival compared with inactive placebo in men with advanced prostate cancer – for whom treatment options are currently limited. The men included in the studies were a specific group:

  • they had prostate cancer that had not responded to previous hormone treatment
  • the cancer was metastatic and had spread to bone or soft tissue, but not to other bodily organs
  • the men had few or no symptoms

Men were either randomised to be given this vaccine, or an inactive placebo. In both studies they found that men given the vaccine survived for around four months longer than men given placebo. Reported side effects with the treatment were fatigue, fever, nausea and vomiting, headache and muscle aches.

Following the results of these studies, the vaccine has been approved by the US and European drug regulation bodies. The vaccine is recommended specifically for the treatment of advanced prostate cancer that has not responded to hormone treatments and has spread to other areas of the body (such as bone), and that is causing the man few, or no, symptoms. NICE is currently assessing whether the Provenge vaccine should be provided by the NHS.

Analysis by Bazian
Edited by NHS Website

Links to the headlines

Life-saving prostate cancer vaccine moves a step closer

The Daily Telegraph, 14 December 2013

Hope for prostate cancer vaccine

The Sunday Times, 15 December 2013

Links to the science

Saif JMS, et al.

A novel prostate acid phosphatase-based peptide vaccination strategy induces antigen-specific T-cell responses and limits tumour growth in mice

Eurpoean Journal of Immunology. Published online December 12 2013