Radioactive bacteria to kill cancer cells
I saw this news alert pop up a couple of places over the past few days, but io9.com had a very nice summary of the research that helped me to get my head around the findings. Researchers at Albert Einstein College of Medicine in New York were examining the use of Listeria monocytogenes as a delivery mechanism for targeting and killing cancer cells in the body, and have published their research in the Proceedings of the National Academy of Sciences. Listeria cases are monitored by the Centers for Disease Control and Prevention, but typically there are only a few hundred cases annually in the United States. Likely this number greatly underrepresents the actual number of infections, as the organism is ubiquitous in the environment, and unless there is an underlying reason relating to the immune system it generally does not cause detectable signs and symptoms of disease. In healthy adults, the innate and adaptive immune system are able to eliminate the organism from the body in short order. If signs of disease are present, treatment with antibiotics is effective, however if the disease is asymptomatic, most experts agree that no treatment is necessary in suspected cases of infection.
The researchers at Albert Einstein thought to take advantage of aspects of the biology of Listeria along with the observation that tumor cells in the body can alter the immune system to allow the cancer to persist. One of the functions of the immune system in addition to keeping us safe from infectious agents is also to help clear out aberrantly growing cells. These are our cells that arise from random mutation of dividing cells, and can lead to the development of various cancers. In some aggressively growing cancers, the tumor cells secrete messengers called cytokines, or stop responding to other cytokines, which have the effect of stopping the ability of the immune system to eliminate them.
Listeria monocytogenes is not a very virulent bacterium; its main virulence trait is its ability to enter and grow inside host cells. Normal immune function generally prevents this from happening in a healthy human, but since cancer cells lower the ability of the immune system to function, the researchers found that these cancer cells were highly infected with Listeria bacteria. Now the bacterium on its own really didn’t do anything bad to the cancer cells, so the researchers thought of a way to make these bacteria more dangerous to the cancer cells–they attached a radioactive molecule to the bacterium. When the cancer cell takes up the bacterium (because it has blocked the ability to fight the bacterium off) it incorporates lethal radiation into it.
Radioactive bacteria were injected into mice with pancreatic cancer daily for a week, with 1 week of rest and then 4 additional injections. The researchers found that the tumors were rapidly infected with bacteria, however normal tissue was not infected at all. Metastatic or secondary tumors were reduced by 90% in comparison to mock treated mice, and primary tumors were reduced by two thirds. Bacteria and radiation were undetectable in the mice a week after treatment, and no other ill effects were noted. These results are extremely promising; pancreatic cancer is one of the most deadly forms of human cancers, with a multi year survival rate of less than 5%. Over 40,000 new cases are diagnosed annually in the US, and the majority of those cases die each year.
Future directions for this research are several-fold. The researchers would like to increase the elimination of tumor killing to 100%, as any tumor left behind after the treatment can metastasize elsewhere in the body, and this event has a poor prognosis for the patient. They are looking to accomplish this by tinkering with genes in Listeria to enable it to be taken up more easily by the cancer cells, by incorporating more radiation into the bacteria, or by altering the injection schedule to make it more effective.
The news alert makes no mention of human trials, as a number of animal studies still will need to be done before human patients might be enrolled into a study. However, with the poor prognosis and treatment options that currently exist for pancreatic cancer, these studies are desperately needed.