With the exception of the HPV vaccine, which is a preventative rather than a therapeutic vaccine, most attempts at formulating a cancer vaccine have fallen flat. Most of the earliest cancer vaccines focused on bolstering the immune system to protect against cancer growth in the body. Sometimes, these vaccines did invoke a strong immune response, but the tumors did not respond, which left researchers frustrated and confused. As a result, many scientists have shifted their focus away from vaccines in the past decade. However, the pendulum could be swinging back in favor of this approach due to the general success of immuno-oncology, which offers a different treatment mechanism.
Immunotherapies like CAR-T gene therapy and checkpoint inhibitors have demonstrated to some researchers that it could be possible to select a vaccine protein target that will make the treatment much more effective. Furthermore, these researchers believe that linking vaccines to existing immunotherapies could have a synergistic effect.
Moving on from the Legacy of the Provenge Vaccine
In 2007, Provenge, a vaccine designed to treat prostate cancer, was rejected by the FDA because of concerns about its true effectiveness. However, the vaccine became the first of its kind approved by the FDA three years later. At that time, its investors expected large revenues in excess of $1 billion. However, the treatment ultimately failed to gain traction because of competing options, its expense, and the time investment required for administration. Today, Provenge continues to be somewhat controversial because it has been shown to merely extend life, not to shrink or eliminate cancer cells.
Researchers have come forward with some ideas about why Provenge is not as effective as its developers had hoped it would be. Because cancer cells have complex mechanisms for avoiding detection by a person’s immune system, the vaccine on its own is not likely enough to elicit the intended effect. However, immuno-oncology has recently developed checkpoint inhibitors, drugs that counter the brakes that cancer cells put on the immune system. Cancer vaccines could prove significantly more effective when combined with these checkpoint inhibitors.
At the same time, combination therapies mean greater risk for the patient. Plus, getting a therapy approved as part of a combination that has not been approved on its own is exceedingly difficult.
The Potential Futures of Cancer Treatment Vaccines
A lot of immunotherapies take advantage of the neoepitopes—unique antigens that are present on the surface of cancer cells. These antigens can distinguish cancer cells from healthy ones. Modern cancer vaccines use these antigens to train the immune system to recognize tumor growth. However, accomplishing this sort of targeted medicine sounds simpler than it really is, because the neoepitopes vary from person to person and from cancer to cancer.
Part of the reason that Provenge did not perform effectively on the market is that it takes a personalized approach, using cells from the patient’s own body to identify targets. This process involves a number of steps and half a dozen appointments. Added to the significant time commitment required is the sheer cost of the process.
The whole picture becomes even more complicated by the fact that tumors are not uniform, so a vaccine for one specific target may not actually work on the whole mass because only part of the surface may express the specific antigen.
When taken together, these issues have pushed researchers to begin thinking about a more globalized cancer vaccine that would not have to be personalized for each patient. Such a vaccine would save significant time and money in the treatment process, but it would have to be administered with another drug, likely an immunotherapy.
Figuring out the Best Path Forward from Here
Because of a long history (more than four decades) of disappointments, a great deal of skepticism about the value of vaccines still exists, even amid renewed interest in this approach. Failures continue to haunt this field. Not long ago, Bavarian Nordic announced that it was giving up on its prostate cancer vaccine Prostvac after analysis of phase 3 trial results. Prostvac uses a pox virus targeted to antigens commonly expressed by prostate cancer. However, the company did not lose all hope. Trials continue to investigate the effectiveness of Prostvac used in tandem with checkpoint inhibitors, and the company believes this approach is worth pursuing.
If the combination trial proves successful, other companies may look more into off-the-shelf cancer vaccines for other common tumors. However, should the trial also be discontinued, it may signal to the immuno-oncology community that personalized vaccines are the way to go. A few other major companies have cancer vaccines under development, so it will be very interesting to see how they perform on their own and in combination with other therapies. In other areas of immuno-oncological research, like CAR-T therapies and checkpoint inhibitors, a single breakthrough triggered a storm of investment and new work. The cancer vaccine field is still waiting for its breakthrough.