Dr. Douglas McNeel is a Professor in the Department of Medicine at the University of Wisconsin-Madison and Director of Solid Tumor Immunology Research within the UW Carbone Cancer Center. Dr. McNeel focuses on prostate immunology and the development of antitumor vaccines as a form of prostate cancer treatment.
Can you give us an overview of vaccines for prostate cancer: which are available now and which are still in development?
Dr. McNeel: If a person has prostate cancer, he usually has surgery or radiation therapy to remove the cancer. These initial therapies cure a majority of patients, but about a third of the time, the disease comes back or resurfaces. We can usually detect the recurrence at a very early stage with a PSA blood test.
Our original thought was that the point of recurrence is the time to intervene, to create a tissue-rejection response.
You can’t really do without a normal kidney. The same is true of the liver.
But you can do fine without a prostate. So if we can create a rejection response to remove any prostate tissue, whether it’s cancer or not, that would be okay.
That was our original thought. The idea with vaccines is to teach the host to generate an immune response that will recognize and destroy cancer cells. But this is a challenge to treat existing tumors with vaccines. With infectious disease vaccines—what we normally think of when we talk about vaccines—we get an immune response that then protects you later on. We call them prophylactic vaccines. But we don’t treat active infections with vaccines. We treat them with therapies that target the bug directly or infuse in an immune system like an adoptive therapy approach.
With cancer, we see the same kinds of hurdles. What we know from animal models is that there are a number of cancer vaccines that can protect animals from cancer, but to get the best response against existing cancers, you have to start when tumors are small and barely detectable. That has been a challenge in pushing those vaccines into human trials.
We’re also learning that when you generate an immune response by means of a vaccination, the cancer can put up a big barrier very quickly to fight against it. Our thought process on vaccines is currently in the midst of changing given that kind of information.
A number of cancer vaccines have been studied over the years. Most of the effort has not produced anything, because we have been looking at vaccines alone, usually in patients with more advanced cancers.
There has been one exception. Provenge (sipuleucel-T), which is a vaccine targeting a protein called prostatic acid phosphatase, was approved in 2010. In this approach, patients have blood removed and their antigen presenting cells are spun out. Then the target of the vaccine, this prostatic acid phosphatase protein fused to an immune-modulating drug, is put together in the lab in the culture dish. The education of the immune system akes place in the lab, if you will. Those cells are then shipped back and infused back into the patient two or three days later. That process is cumbersome, but the approach was shown to be effective.
One large trial led to its FDA-approval. But there were other supportive Phase III trials showing that people who got the vaccine versus those who got a placebo vaccine did better and lived longer. It was a challenge rolling out Provenge (sipuleucel-T) because we don’t see PSA declines with it. We also don’t see changes in the tumors on scans, but we know that men with advanced prostate cancer, in general, live longer if they get that treatment.
Prostvac is an approach that has been in Phase III trials up until recently. Unfortunately, the Phase III trial was deemed to not have met its primary endpoint in September 2017. It did not show that people lived longer. It’s unclear if Prostvac will be developed or not.
Prostvac is a viral vaccine. There is one virus that encodes PSA and then a separate virus. People are immunized with one virus coding the PSA and then boosted with the separate virus. The idea is to use viral vaccines to focus the immune response on the target protein PSA.