Lewis & Brown

There is growing interest in treating men with intermediate or high risk localised prostate cancer with radiotherapy, chemotherapy, hormone therapy or a combination of these to try to shrink the cancer before surgery. Men usually still need surgery after these other treatments, because although they reduce the size of the tumour, they aren’t necessarily curative and tumour grows back and spreads. However, prostate surgery can have distressing side effects like urinary incontinence and erection problems, so Professor Lewis and her colleagues have come up with a way that they hope will make it possible to postpone or avoid surgery for as long as possible after primary treatment.

Their idea is to reprogramme a type of immune cell in tumours called macrophages, so that instead of helping the cancer to grow back after treatment, they will instead fight cancer regrowth. A specific type of macrophage, which expresses a protein called CD206 on their surface stimulate the growth of blood vessels in tumours and tumour relapse after treatment. These cells also help cancer cells to escape into the bloodstream. Professor Lewis’s group has found that these cells are present in human prostate cancers both before and after treatments like chemotherapy or radiation, and they suspect that they may be an important reason why these treatments don’t ‘cure’ high risk localised prostate cancers, so that surgery is still needed.

They think that they can reprogramme these macrophages to express anti-cancer proteins instead. They plan to do this by injecting tiny membrane-bound droplets called liposomes. These will be covered by a protein that is attracted to CD206, so they should attach directly to the pro-cancer macrophages in the prostate, and then release a molecule that makes macrophages start sending out cancer-killing proteins called interferons. These then stimulate other immune cells to attack and kill the cancer cells.

The researchers believe that this might be enough to prevent tumour regrowth after primary treatment. They will check whether this is the case in mouse models of prostate cancer. If they find that they can indeed use such ‘designer’ liposomes to help macrophages prevent cancer regrowth in mice, they will apply for further funding to start a clinical trial of this system in men with high risk localised prostate cancer.

Reference - RIA16-ST2-022
Researcher - 
Professor Claire Lewis and Dr Janet Brown
Institution – University of Sheffield
Award - £397,398