On the TRAIL of a new prostate cancer therapy

This team aims to develop a new type of treatment for advanced prostate cancer, and carry out robust pre-clinical testing to build the evidence needed to take it through to clinical trials. They’ll be carrying out laboratory tests to find out how well, and how safely, a cancer-killing protein loaded into adult stem cells can infiltrate and kill prostate cancer cells in the main prostate tumour and elsewhere in the body.

The backbone of this new treatment is a protein called TRAIL. Cancer researchers have been interested in TRAIL since it was first identified in the mid ‘90s, because it binds to receptors on the surface of cancer cells and induces those cells to commit suicide. What’s interesting about it is that this binding seems to be specific to cancer cells – it doesn’t harm surrounding non-cancerous tissues. However, despite a flurry of research interest and early clinical trials aiming to capitalise on this promising line of enquiry, TRAIL has yet to show any clinical benefit.

The researchers thinks that this is because TRAIL is quite unstable, so when it’s given by itself as a therapy, it degrades before it’s had time to either reach the tumour site or do its job properly. The lead researcher and his team have come up with a way that they think will help overcome this problem. They hope loading the protein into adult stem cells to deliver it to the tumour site will not only stabilize TRAIL so that it can reach the primary cancer but also help it to ‘seek and destroy’ secondary cancers that have escaped the prostate and started to grow elsewhere in the body.

The team has already shown that this system has potential in pre-clinical models of colon and pancreatic cancers, and clinical trials of the system are already underway in lung cancer, which demonstrates that this is definitely an angle worth pursuing.

Now they’ll work out the best way to modify and stabilise TRAIL so that it kills prostate cancer cells effectively. They’ll also test what treatments work best in combination with the stabilised TRAIL, for example docetaxel chemotherapy. The team will investigate if these combinations increase the effectiveness of the therapies, which would mean that lower doses of the chemotherapy can be used.

These tests will use a number of prostate cancer cells lines, and cancer cells from prostate biopsies, as well as some non-cancer cells as controls. Once they’ve got this treatment delivery system fully optimized, they will use animal models of prostate cancer to test the safety of this new treatment and that it works as well as they hope once it moves out of a petri dish and into a whole body system.

Ultimately, they hope to reach a point where it will be feasible to start clinical trials for stabilised TRAIL in advanced prostate cancer.

Grant information

Reference - RIA15-ST2-014
Researcher - Dr Ralf Zwacka
Institution - University of Essex
Award - £255,817