A team of nine Dartmouth Medical School researchers have developed an experimental cancer vaccine that triggers the innate and acquired immune systems. Initial tests on mice suggest the vaccine could be a promising step towards the development of more effective cancer treatment, according to Dartmouth Medical School professor Randolph Noelle, who helped develop the vaccine and experiments.
The human immune system is comprised of two systems -- the acquired immune system depends on previous contact by infection, vaccination or the transfer of antibodies from an immune donor, while the innate system responds to intrusion whether or not it has previously encountered pathogens, Noelle said.
"There are on switches and off switches for each [type of immune system], and over the last decade we've learned what these switches are," Noelle said. "For years people have been trying to build vaccines by turning on these switches."
By triggering the two immune systems, scientists have been able to create vaccines for illnesses such as polio and the measles. Cancer vaccines have failed, however, because cancer does not have typical pathogenic factors, because it is the result of problems within the human cells.
"Your immune system is taught to never respond to self," Noelle said. "But that's only sort of true. We make very low responses to self. So to concoct a vaccine, the thing that stimulates the vaccine needs to be extremely strong to overcome the low response to self."
Cancer vaccines work by heightening the body's natural response to irregular cell growth. While many of the cancer vaccines currently in clinical trials focus on only one immune system, Noelle's experimental vaccine triggers both. The research team has found that this approach provides far more effective results than vaccines that trigger a single system.
In the experiment, mice were injected with melanoma cells. Melanoma is a malignant tumor of melanocytes, which are predominantly found in the skin. Researchers gave some of the mice vaccines that triggered either the innate immune system or the acquired immune system, and others the newly developed vaccine that triggered both. The mice that were treated with the vaccine that triggered both systems survived 47 days, while the mice given vaccines that triggered the innate or acquired systems survived for 30 days and 35 days, respectively. The mice treated with Noelle's vaccine also developed more cells involved in the immune system's long-term memory, which helps defend against a recurring cancer.
A vaccine that magnifies the immune system's reaction to it's own cells also presents dangers for other non-cancerous cells in the body, Noelle said. For example, the black mice used in the experiment turned white after being administered the vaccine, since non-cancerous melanocytes were destroyed along with the melanoma, resulting in the absence of melanin and, therefore pigmentation.
The vaccine could be worth these downsides, if it proves to be a successful preventative measure for high-risk individuals or as treatment for people already suffering from cancer, Noelle said.
"Immunity to cancer will inevitably trigger some sort of autoimmune disease," Noelle said. "When your choice is stage 3, stage 4 melanoma, and you'll be dead in a few years or you'll have to deal with autoimmune compromise, maybe, it's really the better option."
The cancer vaccine will not necessarily compromise the body's immune system, as some cancers have distinguishing factors from their normal cell counterparts, making them easier to treat and eradicate, he added.
A vaccine that enhances the immune system's natural response would not be limited to the treatment of cancer, Noelle said. A heightened immune response could be used to fight other diseases that are particularly difficult to treat, specifically chronic viral diseases such as HIV, he added.
Though the vaccine has proven to be effective in mice, it remains to be seen if the results will translate to humans. Noelle hopes to create a similar vaccine that can be used in clinical trials and said he is optimistic about the potential capabilities of a cancer vaccine that activates both of the body's immune systems.
