26 February 2016
By Dr Wendy Winnall - PCFA Research Team
The recently publicised success of modified T-cell therapy in the treatment of acute lymphoblastic leukaemia (ALL) has been described by the press as miraculous. If the therapy continues to perform as well as these first trials, this claim, for once, is justified. ALL is a terrible cancer with a low survival rate in adults, so any treatment that improves survival is urgently needed. T-cell therapies are a major breakthrough in that they are a whole new form of treatment. T-cell therapies are one of many types of immunotherapy currently being developed to treat cancers. In 2013 cancer immunotherapy was named the "breakthrough of the year" by the highly-rated journal Science. So can we treat prostate cancer with T-cell therapies?
Modified T-cell therapies involve taking T-cells, a type of immune cell, out of a cancer patient, modifying them to target the cancer cells, then infusing them back into the patient. These T-cells then find and kill the cancer cells, in a similar way to killing cells that are infected with a virus. A remarkable feature of this process is that it provides a memory for the immune system that can last many years, similar to how a vaccine works. We’ve recently seen wonderful results for ALL, but as each different cancer is a different disease, a different form of T-cell therapy needs to be created and optimised for each cancer.
There are a number of reasons that prostate cancer might be a good candidate for T-cell therapies. The most important requirement is a molecular marker that can be used to tell the difference between tumour cells and normal cells. This marker is used to re-educate the T-cells, making them target the tumour. Two protein markers, called PSMA and PSCA, seem to be able to do this in prostate cancer, and initial experiments have been promising. Another positive is that the prostate is not essential for life and is usually removed by surgery for advanced prostate cancer. So a therapy that may harm prostate cells is acceptable, which would not be the case for liver or lung cancer.
Unfortunately there are a number of roadblocks that make prostate cancer a more challenging target of T-cell therapy. Prostate cancer is a solid tumour, unlike the leukaemia ALL, where the cancer cells circulate in the blood. The most dangerous stage of prostate cancer is bone metastasis, where the cancer spreads and forms new solid tumours in the bone marrow. It’s these tumour cells that most need to be destroyed. Modified T-cells will need to “migrate” into these tumours to get access to the cells they need to kill. Solid tumours are also more difficult to treat with T-cell therapies because they modify their environment by secreting proteins that stop the action of T-cells. A recent academic review of T-cell therapy research for prostate cancer has a list of potential modifications of this technique, that would help make it more effective. These include:
- adding specific "tracking proteins" (called chemokine receptors) to the T-cells to help them move into the bone marrow tumours
- treatment with drugs to improve the blood vessel access for T-cell migration into bone marrow tumours
- blocking the activity of proteins in the tumour that inhibit the action of T-cells
- androgen deprivation therapy may render the tumour cells more sensitive to killing by T-cells
A lot of basic research, using mice and cells growing in the laboratory, will be necessary before a suitable prostate cancer T-cell therapy can be tested in clinical trials. We also need to be very careful of toxic side effects, which are difficult to predict for new therapies.
Modified T-cell therapies are one form of cancer immunotherapy. Immunotherapies act by increasing or decreasing immune responses to treat disease. Other forms of immunotherapy are already used to treat cancer with great success, such as the antibody Herceptin for breast cancer. Therapeutic vaccines are also being trialled for prostate cancer with recent good results giving us hope. One example of this research in Australia, funded by PCFA and The Movember Foundation is the work being conducted by Assoc. Prof. Kirsten Radford at the Mater Medical Research Institute in Queensland. Dr Radford is working towards an ‘anti-tumour vaccine’ that supports a person’s immune system to eliminate cancer cells throughout the body. A successful immunotherapy for metastatic prostate cancer will certainly be a dream come true.