11 April 2016

By Dr Wendy Winnall - PCFA Research Team

For over a decade, scientists have been hard at work developing therapeutic vaccines that can stimulate immune responses against cancers. Unlike traditional vaccines that prevent disease, a therapeutic vaccine will be a treatment that tells the immune system to attack the tumour, as if it were an infectious disease. Like so many journeys in research it’s been a long and bumpy road, but we are now closer than ever to having a successful prostate cancer therapeutic vaccine become part of the mainstream treatment for this disease.

In fact, the very first therapeutic vaccine for cancer to be approved by the US FDA was a treatment for prostate cancer. In 2010 a company called Dendreon gained approval for their vaccine sipuleucel-T (Provenge®). This treatment involves removing a sample of immune cells from a patient, modifying them in the laboratory, then infusing them back into the patient in a series of treatments. It is the only personalised treatment for prostate cancer that is clinically proven to work. Sipuleucel-T is approved in the US for treatment of men with metastatic castration-resistant prostate cancer, starting at the asymptomatic stage.

Clinical trials showed that this therapy lead to an increase in average overall survival of 4.1 months. Although this may seem like a modest increase, this time would be quite valuable to men who have exhausted all other treatment options for their metastatic prostate cancer. Unfortunately the massive price charged for the treatment (over $100,000 a year in the US), as well as questions over its actual effectiveness for patients, and the decision not to subsidise its cost, are all likely to have contributed to its limited use. It has not been approved by the TGA for use in Australia.

This has been an important lesson, both for researchers and for the pharmaceutical industry. Therapeutic vaccines for prostate cancer need to be sufficiently affordable and effective to ensure their widespread use.

The good news is that there are a number of other therapeutic vaccines for prostate cancer currently in clinical trials that we hope to be much more effective treatments. A recently-completed phase 2 trial in Japan has also shown promising results. This new therapeutic vaccine is simpler than sipuleucel-T, as immune cells do not need to be taken out, modified and put back in to patients. The Japanese study tests a treatment called personalised peptide vaccine immunotherapy. The researchers have established a series of 24 peptides (protein fragments) that can be used to stimulated immune cells. The vaccine tells the immune system that it should mount an immune response against a "threat", using the peptides to identify that threat.

The treatment starts with a blood test to ask which of the peptides will be most effective for each patient. Based on these results, four peptides are combined into a vaccine, which is administered in a series of six injections. The patients in this trial had metastatic castration-resistant prostate cancer and were treated before chemotherapy. Those that received the vaccine treatment had an average PSA progression-free survival of 22 months, which was significantly longer than the control group, at 7 months. The overall survival for the treated group was a fantastic 39 months longer than the control group.

Fortunately the side effects of the treatment were minimal. Although this is a small study, and phase 3 trials are needed to ensure these numbers hold up, this treatment looks extremely promising. It’s a far simpler procedure than sipuleucel-T, so it will hopefully be less expensive and the effect on life-expectancy will be far greater.

The personalised peptide vaccine treatment should soon enter phase 3 clinical trials, joining other prostate cancer vaccine candidates such as DCVAC, Prostvac and ProstAtak. There are also clinical trials underway for combination therapy, where vaccines are combined with other treatments such as androgen deprivation therapy, chemotherapy or radiotherapy.

Since the 2013 announcement that cancer immunotherapies were the "breakthrough of the year" by the preeminent journal Science, investment in therapeutic vaccines has soared. This investment is crucial for the expensive phase 3 trials and applications for approval from regulatory bodies such as the FDA. As a consequence, we hope to soon have successful immunotherapies for metastatic prostate cancer, where the power of a man's own immune system can be harnessed to join the fight against this disease.