On April 29, 2010, the Federal Drug Administration (FDA) approved the first ever cancer vaccine, a treatment that trains the body's own immune system to fight cancerous tumors in the prostate. The vaccine, called Provenge (generic name sipuleucel-T), was developed by the Seattle-based biotech company the Dendreon Corporation. A handful of similar cancer vaccines have been approved for use in other countries; Provenge is the first to be approved for use in the United States.
Provenge is a customized immunotherapy treatment that sensitizes each patient's immune system to their own tumor. Provenge is a procedure – not a drug. Certain white blood cells, called dendritic cells, are separated out of the patient's blood. Then protein cells from the patient's tumor are isolated and incorporated into the dendritic cells, along with an immune system booster. This forms the "vaccine," which is then infused back into the patient's bloodstream. Once back in the patient's body, the treated dendritic cells educate the patient's immune system to better fight off the cancerous tumor.
According to Dendreon, the procedure will cost about $93,000 per patient. The high price comes as no surprise; other cancer drugs currently available are similarly priced. For now, Provenge will only be available in 50 cancer treatment centers, all of which were approved Provenge clinical trial sites. However, now that Provenge has been approved, Dendreon is expected to ramp up their capacity. In six to twelve months, experts predict that Provenge will be available to all patients who would need it.
The technology used by Provenge was first discovered and began development 20 years ago. But the treatment process was only approved to treat advanced prostate cancer after a recent large-scale clinical trial involving 512 men. The trial was highly successful; the drug extended the lives of patients an average of four months when compared to a placebo. To put that number in perspective, three years after the trial began, approximately 33% of men given Provenge were still alive compared with fewer than 25% who received a placebo.
The approval comes after years of (often bitter) debate over Provenge's effectiveness and safety. Many experts – including Dr. Edgar Engleman, one of the innovators of the treatment method – adamantly believe that not only is Provenge safe, but it is revelatory in its overall harmlessness, especially compared to other late-stage cancer treatments. Experts like Dr. Engleman believe that the approval of Provenge may in fact herald a new wave of cancer treatments that will not necessarily come with the many negative side effects typically associated with chemotherapy and radiation therapy.
Healthline talked to Dr. Engleman, who helped us understand how the treatment works, and what the FDA approval means for the future of cancer treatment. Dr. Engleman is a pathologist and researcher who is the director of the Stanford Blood Center at Stanford University in Palo Alto, Calif.
Healthline: Where did the idea for this new cancer treatment come from?
Dr. Edgar Engleman: My role was on the discovery side. I'm a cellular immunologist, and the research we do here at Stanford in my lab is devoted to better understanding how the human immune system works and, in particular, how certain cells called dendritic cells work. We discovered about 20 years ago that we could isolate these cells in humans, and we were able to show in test tube experiments that they had unique abilities to process and present substances from tumors to the immune system in vitro. In other words, we could vaccinate the immune system in a test tube, which suggested that these were very powerful cells indeed. And the in vitro test tube experiment led to the idea that perhaps we could use the same cells to vaccinate against cancers in people. And that's what we pursued beginning in the early 1990s.
HL: Why was prostate cancer decided upon?
EE: Well, as it turns out, it could have been prostate, breast, colon, lung – any of these types of common tumors. The idea was to try to attack a common tumor for which there were little or no other options available. Beyond that, the company could only afford to research one at a time because it was so expensive to develop this kind of technology. One of the reasons prostate cancer emerged as the top priority was that if you attack a tumor in the prostate, and kill normal prostate cells in the process, it's not going to hurt the patient in a big way because the prostate gland is not required for normal living. It's not like you're attacking vital organs such as the heart or the lungs or the liver.
HL: Are there plans to apply this approach to other types of cancer?
EE: As long as you have access to the right antigens – the substances from the patient's tumors – you should be able to prepare dendritic cells and use them in the same manner. However, that approach would have to best tested for each tumor. So the FDA would require that for any given cancer vaccine, you'd have to test that particular vaccine in the targeted patients before they would give approval.
Besides a new treatment option for patients with prostate cancer, Prevenge demonstrates that this kind of approach can work. This breakthrough procedure means there will be other related approaches that hopefully will be even more potent. The FDA approval really opens the door and gives researchers a license to go out and do this in even better ways.
HL: This process is being described as a vaccine, but it's not the type of vaccine most people are used to. How is it different?
EE: Vaccines are historically and traditionally used to prevent disease or infection. We call these prophylactic vaccines, and they're given before an individual is exposed to a potentially infectious virus. During this treatment, we're giving the vaccine after the disease is already manifested. The reason it is appropriate to call it a vaccine is because we are activating the recipient's immune system against something else, as opposed to giving them something that acts on its own.
When we give a patient a chemotherapeutic agent, for example, those agents act on their own. They don't require the patient's immune system to become activated. Here, we are actually calling the immune system to arms, which is exactly what we do with a preventative vaccine. The main difference is that we're not trying to generate an immune response against an infectious agent; we're generating an immune response against a tumor.
HL: Dendritic cells play a key role in this vaccine. What is their normal role in the body?
EE: When you get an infection, dendritic cells become sensitized to that infectious material, and they educate the rest of the immune system and cause it to go into action and fight the infection. For the most part, dendritic cells in the skin and organs just sit there. But if something comes along that shouldn't be there, they get very excited. They leave their posts and travel into the lymphoid organs and incite the immune system to go and attack the foreign substance.
HL: So how does Provenge use dendritic cells used to fight cancer?
EE: Dendritic cells are isolated and removed from the patient. Then, proteins from the patient's cancerous tumor are added to the dendritic cells, which have the special ability to take up the material, process it, and then present it to other immune cells in a way that encourages them go out and attack the tumor. When these dendritic cells that are armed with the tumor substances go back into the body, they basically instruct the immune system to go out and kill the tumor. Without the dendritic cells doing this, there can be no mounting of this kind of attack. And it's a very specific attack that causes little or no collateral damage. It's not like a dirty bomb, like chemotherapy that kills everything in its way.
HL: It seems like Provenge is a game changer. Will it change the way that cancer is treated in the future?
EE: I hope so. This is a radical new approach. It seems to be a very safe approach, and this is the first time it has been shown to work, which means it will lead to a whole other array of like approaches that people can build upon without being concerned that it can't work. For the past 100 years, most people would have said 'this could never happen, it's too difficult.'
HL: Do you think the newness of this was one of the reasons there was so much trouble securing FDA approval for it?
EE: Absolutely; there's no question about it. It's so completely different than a typical drug. First of all, we're using the patient's cells, so we can't put this treatment into a bottle and give everyone the same drug. My cells wouldn't work for you, and your cells wouldn't work for me. The FDA had never seen anything like this, so they had to educate themselves, and that took a very long time. I wish the FDA would have approved it several years ago when they first had the opportunity to do so, but even after their own advisory committee said that they should, they didn't. I think they just wanted more proof because this was such a new approach. They made the company do a third trial, and it was very successful.
HL: It seems amazing that it has been 20 years that the discovery was initially made.
EE: Tell me about it.
HL: In those two decades, have you seen progress made elsewhere that has built upon or might work with the technology Provenge uses?
EE: Absolutely. Provenge is using technology that we discovered 20 years ago. In the meantime, there has been a lot of great research that has been done on the immune system. We know much more about the biology and life cycle of dendritic cells. This is going to make it possible to target the cells within the body, so you don't necessarily have to remove them and manipulate cells at great expense. So yes, I think there has been a lot of work that has taken place during those two decades that should lead to improved therapies based on the same principles. It could have gone faster had Provenge been approved sooner, but nonetheless, there has been a lot of work that has taken place that will lead to better forms of this kind of therapy.
It's a nice ending. It's been really exciting, and I think it means good things are ahead. It's been very gratifying for me personally and for the researchers here at the Stanford Blood Center. And I hope for more good things in the future.