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Spring 2010 Letter from the Editor
The field of medicine made a pivotal turn over 200 years ago with the development of vaccines for several reasons. First, it was a reaffirmation of science over superstition when it came to human health, setting medicine on a technologic trajectory. Second, it affected essentially everyone in the population since diseases like polio knew no geographic or social boundaries and had devastating consequences. Finally, it was a comforting medical advance in that it harnessed the body’s own immune power—it used the ultimate “natural” approach.
It follows that the immune system would then be asked to cure cancer. After all, it is a logical progression that unwanted intruders within could be repelled by the same system that, once “educated” by the right vaccine, eradicated smallpox. In fact, numerous folk medicines and new age and alternative medicine have claimed an immunological benefit—a mechanism that resonates with the public. Likewise, the government and private industry have invested billions of dollars in new immunological approaches to treating cancer. Why, after decades of cancer vaccine research, have none been approved by the Food and Drug Administration?
Not too long ago, many were declaring that the field of cancer immunology was a dead end after initial excitement led to numerous failures. However, several fundamental hurdles have been overcome, and the possibility of a successful cancer vaccine is at our doorstep.
“Getting Personal” provides some historical and scientific reasons why the road travelled once for viruses and bacteria is much more fraught with obstacles when the objective is cancer. The difficulty lies in the complexity of our immune system, which is tightly regulated to avoid autoimmunity—that is, a reaction against proteins and other components of our bodies. When that regulation, also known as “tolerance,” is broken, autoimmune diseases, such as lupus or rheumatoid arthritis, can erupt.
The main step to devise successful cancer vaccines has been to find cancer-specific targets—proteins or other substances that would single out cancer cells. However, since cancer cells originate from normal cells, it is nearly impossible to develop a target that is not “self.” So the next barrier is to delicately maneuver the feedback mechanisms to allow a vigorous immune reaction to cancer cells.
Several fundamental hurdles have been overcome, and the possibility of a successful cancer vaccine is at our doorstep.
You will read about clever strategies that have required scientists to stretch the limits of knowledge regarding the molecular and cellular details of the normal immune system, and how it actually does recognize cancer, but only mounts a muted response. Provenge, a prostate cancer vaccine under review by the FDA, and BiovaxID, a lymphoma vaccine that is not too far behind, use different technologies: one overcomes the tolerance problem and the other addresses the creation of a unique protein target.
It is not clear that there is one right answer to what will make an effective vaccine. It may be that different cancers require different vaccine strategies. As with other targeted therapies, there is no substitute for basic science discoveries to lead the way for well-informed experimental trials. Assays that measure anti-cancer immune reactions have to be designed to find out if the vaccine even stands a chance. Vaccine regimens almost always evolve through many versions as they are continually refined.
More projects by “big pharma” and small start-up biotech companies as well as academic centers are turning the corner from the lab to the clinic. While the effectiveness of the immune response will always be the limiting factor, finding the right timing and the right target using the right agent is becoming more likely than the long shot it once was.