PA12-01 Galustian Lay summary Principal Investigator: Dr Christine Galustian, Senior Research Fellow at King’s College London Lay title: Developing a new localised immunotherapy for advanced prostate cancer. What are you proposing? We are proposing a new minimally invasive treatment for advanced prostate cancer that can boost the immune system to kill prostate cancer cells. Why are you proposing it? The current available treatment for targeting the immune system (Provenge™) is only available for patients who have late stage prostate cancer. The treatment can prolong life, but only for a few months. This is thought to be because firstly, at this late stage of prostate cancer, the immune system is already weakened and cannot respond as well to a treatment which is attempting to boost its response to the cancer. Secondly, the treatment is not targeted to the prostate area where the immune system is most weakened. How are you proposing to do it? There are a group of proteins known as cytokines, which can boost the immune system to help combat and destroy cancer cells. These cytokines are injected into the blood and can go freely around the body to activate cells of the immune system to kill tumour cells. However, they are also toxic and can give bad side effects such as septic shock (infection leading to serious low blood pressure). Another group of immune system therapy proteins currently used are antibodies. These proteins block the effect of one type of white blood cell (regulatory T cells) which prevents the immune system’s ability to fight cancer cells. These are also toxic and can cause autoimmune reactions. We are going to modify a set of the above proteins to give them an additional molecule known as a “tail” that can attach to the surface of cells and tissues. When these drugs are injected into the site of a tumour, they will stick there and boost the immune system to destroy cancer cells. The ability of these drugs to stay at the site of the cancer means that they will be less toxic to the patient than normal immune system therapy agents which circulate around the body and therefore cause fewer side effects. Once the immune system is activated by these drugs it will then be able to kill any nearby prostate cancer cells and also those cells that have also spread away from the prostate. How long will it take? To show that the immune system therapy agents can activate the immune system to destroy prostate tumour cells and are safe to use in an animal model will take one year. What is the budget? £49,932 Prostate Cancer UK is a registered charity in England and Wales (1005541) and in Scotland (SC039332). A company limited by guarantee registered number 2653887 (England and Wales). Why is this project suitable for a pilot award? Anti-cancer immune system therapy proteins have not been modified in this way before. We need to prove the concept that this therapy would deliver better results for patients and be less toxic than conventional immune system drugs before we can use them in patients. What are the expected outcomes? We expect that the tailed immune system drugs will be much more successful at destroying prostate cancer cells than the current non-tailed cytokines available and they will be effective at very low doses without giving harmful side effects. How could it make a difference to the lives of men affected by prostate cancer? Current treatments for men with advanced prostate cancer give many side effects and resistance of the cancer can develop to normal hormonal therapies. A treatment that can help eliminate the cancer by boosting the body’s own immune system without any side effects to the patient could be used with hormone therapy or even on its own, if proved very effective, as an alternative treatment to stop the disease spreading further and saving many lives. Please write a summary of the project in one sentence only. This project will investigate the effectiveness of a new immune system agent that can be localised to the prostate to eliminate the cancer cells without any side effects.