Immunotherapy for Prostate Cancer – Dr Nicola Annels

There is an unmet need for the development of immunotherapeutics which use the body’s own immune system to target only tumour cells leaving normal cells untouched. This means a much more efficient therapy and fewer side effects for the patient.

Cancer immunotherapy is one of the newest and most promising of cancer treatments. Simply stated, immunotherapy is a type of treatment that helps/boosts the body’s immune system to attack cancer. As cancer cells have the ability to evade the immune system by using a number of clever techniques, immunotherapy is based on understanding these techniques and developing strategies to restore the immune system’s ability to destroy tumours. We have several lines of research that aim to understand and overcome the major mechanisms that tumours use to suppress the immune response.

Our groups use of oncolytic viruses help to ‘kick-start’ immune reactions against infected and uninfected tumour cells. In addition, in response to viral infection, cells within the tumour microenvironment produce an array of immune-stimulating molecules called cytokines. This changes the tumour microenvironment from a suppressive environment to a pro-inflammatory one, attracting additional immune cells into the tumour.

In some cases tumours are capable of recruiting immune cells that are helpful to the tumour. One of these cell types is called regulatory T cells and they work to reduce the immune response around the tumour. One of our current lines of research is developing a novel agent to target these regulatory T cells. In preclinical work in the lab we have shown that our agent is able to disrupt the function of these regulatory T cells and leads to enhanced immune responses.

Another mechanism that the tumour uses to turn off the immune response is using normal checkpoint pathways used by the body’s immune system as ‘brakes’. By using these signals the cancer can shut down any attack by the immune cells. Blocking the effect of these checkpoint pathways can restore the normal function of the immune cells. We are currently working on a Prostate Cancer UK funded project to look at combining oncolytic viral therapy and immune checkpoint blockade to achieve an optimal prostate cancer therapy. This approach aims to stimulate the immune system with a live virus to start the process (ie killing of the cancer cells) then combine with checkpoint blocking drugs to sustain a long-term immune control of cancer.

Finally we are also studying another phenomenon that occurs to particular immune cells within tumours which is T cell dysfunction as a result of exhaustion. When T cells are exposed to a chronic stimulation e.g.by the presence of a tumour, along with all the other inflammatory signals they receive these components drive T cells to literally become ‘exhausted’ –ie lose their ability to carry out their normal killing function. We are studying this phenomenon in a range of different cancer types and investigating ways to achieve optimal recovery and function of the T cells – crucial for eliminating the tumour.