The term ‘failure’ may no longer apply to cancer vaccines according to a recent article in Marketwatch. Researchers have endured over four decades of frustration since the first two therapeutic vaccines were approved but then seldom used.
Years ago vaccines simply bolstered the immune system to attack cancer cells. The immune system was stimulated but the researchers were not able to determine why the tumors did not shrink.
The case for vaccines has been given a boost by the successful performance of immunotherapy, which now gives new hope to cancer patients.
New Evidence of Patient Survival
Checkpoint inhibitors have been responsible for patient survival in cancers that were previously difficult to treat.
A patient’s cells can now be re-engineered by CAR-T cell therapy to fight cancer.
Researchers now believe that they have found a new approach to solving the obstacles presented by resistant tumors. That would involve choosing a protein target. There is also increasing interest in the combination of new therapies together with cancer vaccines to improve that potential.
About Antigens
Proteins called antigens which are bound to cancer cells can identify normal cells versus cancer cells. Cancer vaccines make use of antigens by training the immune system to identify abnormalities and attack them.
Initially, in the early stages of vaccine development, the scientists concentrated on antigens naturally found in the body. Then, with the advent of genome sequencing (decoding), it was easier and less costly to study antigens called neoepitopes that trigger T cell responses.
If you compare personalized treatment with the average “off-the-shelf” vaccine, the “off-the-shelf” method would provide ease of therapy and less cost to develop.
About the First Vaccine
In 2007, Provenge was a promising but controversial vaccine developed to treat prostate cancer. Yet the cancer community erupted upon hearing that the FDA did not approve Provenge due to concerns over its effectiveness.
The outrage spilled over into newspapers, online complaints by its developer, threats directed at researchers, and even calls for an investigation of the FDA’s decision.
Finally, in 2010 Provenge became the first cancer vaccine to be FDA approved. Wall Street was enthralled. Estimates were that it will be worth over $1billion per year in revenue.
However, there were several factors that led to Provenge’s dwindling sales and eventual bankruptcy. First there was the cost of the treatment which amounted to $93,000. Second the vaccine faced serious competition from other new cancer vaccines.
Provenge had been designed using the personalized approach. To develop the vaccine, the patient’s blood cells must be sent out to a lab where it is processed, returned then reinfused over a period of six doctor visits. This is a customized and costly process.
The concept of the personalized approach is further complicated because tumors are not uniform. For that reason developing a vaccine for one target might not have an effect on tumor as a whole.
Provenge is now being sold by Sanpower Group, Nanjing, China. Although the clinical trial that brought approval to Provenge resulted in patients having overall survival of four months, there was no evidence that the drug eliminated or even reduced cancer cells.
Scientists have come up with new information that explains the lack of response from Provenge. Cancer cells are able to stop or “brake” a natural immune response.
Then, in 2010, checkpoint inhibitors emerged that fight cancer by countering the “brakes” that have been put on the immune system. Combining checkpoint inhibitors with cancer vaccines could be the key to success.
It is conceivable that at a later date vaccines may also be able to prevent relapses.
A More Recent Example
According to a 2017 article in FierceBiotech, the Danish based Bavarian Nordic’s efforts to complete its Phase 3 clinical trial for Prostvac had run into continuous delays.
Prostvac is a prostate cancer vaccine that instructs the immune system to identify prostate-specific antigens.
Phase 3 began in 2011 with a two-year goal of completing enrollment. Although it was encouraging to learn that patients had “died at slower rates than expected”, that good news actually prolonged the trial. Delayed trials are not always successful trials.
As it turned out, in 2017 an independent Data Monitoring Committee ruled that the Phase 3 trial of Prostvac should be discontinued.
Then in 2018, Bavarian Nordic announced its co-sponsorship of a Phase 2 study of Prostvac with Bristol-Myers’ Nivolumab and Opdivo. The patients would receive Prostvac with either Nivolumab or Opdivo or a combination of all three. The trial is ongoing.
Despite the Setbacks
In spite of forty years of slow growth, the last decade has produced significant achievements in immunotherapies. A total of 1,195 clinical trials for prostate cancer are currently active.
These trials are studying monotherapies and combination therapies involving immunotherapies and radiation, chemotherapy, and androgen suppression therapy.
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