Cancer is a demon that doctors have desperately tried to exorcise for decades. It is the body turned against itself, where the natural programming of healthy cells runs amok. The dysregulation of the orderly signaling pathways is linked to the balance between cellular growth and cellular specialization of the cell life cycle. The result is unrestrained cellular proliferation accumulating into large tumors that interrupt the normal functions of vital organs.
Since cancerous cells are derived from normal cells of the body, the human immune system does not see them as disease because the immune system is trained only to distinguish between “self” and “non-self.” This prevents the body from attacking itself, though disorders where this mechanism fails are known as autoimmune diseases.
A recent study published by Tanyi et al. (2018) in Science Translational Medicine appears to have made a breakthrough in this area, where a successful ovarian cancer vaccine was produced and clinically evaluated that was personalized to each patient.
The human immune system can be basically divided into two parts: a non-specific initial response and a highly specific follow up response. When a foreign disease-causing agent or pathogen invades the body, the first line of defense is immediate and not targeted exclusively to the particular pathogen. This is merely a stop-gap measure to keep the pathogen at bay until the secondary adaptive response can be formulated by the body to eliminate the invader either through antibody producing B-cells or killer T-cells.
Once the disease agent has been thwarted, the adaptive immune system “remembers” the solution in the form of memory cells. This way, if the body encounters the same pathogen again, it will recall the tool used to combat it and can promptly deploy a solution. This is the basis behind vaccines: to introduce the immune system to a pathogen in a safe and controlled manner, so it can develop a suitable response and will remember how to react should it come across that pathogen again.
Edward Jenner was able to deduce that there was a subpopulation of people that survived smallpox infections who had previously been exposed to a related virus: cowpox. Cowpox was capable of infecting and replicating in humans, though the symptoms were much milder and the human immune system could easily adapt and clear the virus, unlike its human counterpart. And those persons exposed to cowpox did not succumb to the brutal effects of smallpox; somehow these people were protected. Thus, Jenner posited that if people were inoculated with cowpox that they would be protected against smallpox.
This strategy represented the first recorded instance of a vaccination program. Cowpox was found to be sufficiently similar to smallpox, that the memory cells of the immune system could be tricked into seeing smallpox as cowpox. The scientists of the current study have endeavored to trick the immune system into recognizing certain cancers as foreign, thus triggering the immune response.
The notion of vaccinating against different forms of cancer is complicated by the fact that the disease is propagated by a person’s own cells, which are treated as “self” by the immune system. Therefore, research scientists have sought to trick the adaptive immune system to seeing cancer cells as “non-self” and thus attack them. The key has been to identify features of cancer cells that are distinct from normal cells so that tumors are targeted while non-malignant cells are safe from a cross-reactive autoimmune reaction.
This is where the current study on personalized ovarian cancer vaccination comes in: where the scientists looked for ways to stimulate an immune response to what are known as “neo-antigens.”