Immunotherapy for Prostate Cancer

The immune system protects us by recognising and attacking things which might make us ill, such as viruses, bacteria, or unhealthy cells.

One of the reasons cancer is so hard to treat is that cancer cells are very similar to our normal, healthy cells. This makes it difficult for our immune systems to recognise them as an enemy, and difficult to design drugs which can tell the difference between cancer and healthy cells.

Immunotherapy is one of the most exciting scientific advances in recent years. The idea is to retrain the immune system to identify and attack cancerous cells.

Although immunotherapy treatment is available, it hasn’t been very effective so far. The only immunotherapy treatment for prostate cancer we have at the minute involves taking the patient’s blood, reprogramming his white blood cells to attack cancer cells and transplanting these cells back into his bloodstream. This treatment does not reduce symptoms or shrink tumours. It’s also a long and expensive procedure, not provided by the NHS.

PCRC scientists, led by Dr Christine Galustian at King’s College London, are working with a naturally-occurring protein called IL-15. IL-15 causes the immune system to identify and attack cancerous cells. However, getting this protein to the site of the cancer is difficult. When it is injected into the bloodstream it doesn’t effectively fight cancer, and has toxic side effects.

Dr Galustian has devised an innovative new way to harness IL-15’s immunotherapeutic properties. She uses ‘chemical tails’ – an extra molecule made of peptides and fatty acids – which can be attached to the protein. This tail anchors the IL-15 at the cancer site, meaning it can help the immune system destroy the prostate cancer without harming the rest of the body.

Dr Galustian’s research has already seen startling results – it has reduced tumour growth in model organisms by 60% using this method. She anticipates the new treatment will be even more effective in humans. This is because the IL-15 that she has used in the models will work even better in humans as it is a human protein. With continued support, these exciting clinical trials could take place as early as next year.

Thanks to additional PCRC funding, a new chemistry technician will shortly be joining the project. The new team member will experiment with different agents which, when used together with IL-15 in certain patients, will maximise its clinical potential.

If successful, the outcome will be a new immunotherapeutic treatment for men with advanced prostate cancer, but the therapy could have wider implications for fighting all sorts of advanced cancers, and for moving patients away from invasive and difficult treatments like chemotherapy.

PCRC has commissioned several companies, including Genescript to produce purified IL-15.

Immune checkpoint blockade – a treatment for urological cancers?
Elhage, O., Galustian, C. & Dasgupta, P. Oct 2016 BJU INTERNATIONAL. 118, 4, p. 498-500

Cathepsin-L and Transglutaminase Dependent Processing of ps20: A novel Mechanism for ps20 Regulation via ECM Cross-Linking
Hickman, O. J., Dasgupta, P., Galustian, C., Smith, R. A. & Vyakarnam, A. Sep 2016 Biochemistry and Biophysics Reports 7, p. 328–337

Expression of two WFDC1/ps20 isoforms in prostate stromal cells induces paracrine apoptosis through regulation of PTGS2/COX-2
Hickman, O. J., Smith, R., Dasgupta, P., Rao, S. N., Nayak, S., Sreenivasan, S., Vyakarnam, A. & Galustian, C. 26 Apr 2016 British Journal of Cancer p. 1-8