Boosting Cancer Treatment

Tetanus Booster May Help Boost Cancer Therapy
Tetanus Booster May Boost Brain Tumor Treatment

March 25, 2015 
A cancer vaccine would be as beneficial as it is problematic to develop. Vaccines work by training the immune system to recognize and destroy a foreign invader. The trouble with tumors is they are made of human cells gone haywire, and the immune system often has a difficult time telling the difference between a cancer cell and a healthy cell.
That does not mean, however, that vaccines and the immune system are not useful in the fight against cancer. Human Papilloma Virus (HPV), which can cause cervical, throat and other cancers, is preventable by vaccine.
Other cancers have specific markers or associated viruses that set them apart from normal human cells, so the immune system can learn to attack them. One such cancer is glioblastoma, an extremely aggressive brain tumor that kills half of those who have it in less than 15 months.
Glioblastoma cells contain a virus called cytomegalovirus that healthy brain cells do not, and scientists have begun taking advantage of this fact and the immune system’s capacity to recognize and kill an invader to treat glioblastomas. Now Duke University neurosurgeons have discovered a way to further take advantage of the immune system with a tetanus shot, and improve how the immune system attacks glioblastoma.
The study, which appeared in the journal Nature, provided 12 glioblastoma patients an extra injection on top of their immunotherapy. Six received a tetanus booster, while six received a placebo.
Dr. John Sampson, the lead author of the study, said the combined immunotherapy and tetanus booster increased the median survival time from 15 months to almost five years. One patient in the tetanus booster group is alive and shows no tumor growth after eight years.
The researchers performed several parallel studies in mice to determine exactly how the tetanus shot boosted the immune response, specifically how the tetanus shot gathers special immune cells, called dendritic cells, in the lymph Artist Rendering of Dendritic Cellnodes.
The adaptive immune system — what vaccines work with — conditions the immune system to recognize a specific piece of an invader called an antigen and develop a molecule to latch onto it called an antibody. Once the immune system recognizes an antigen it signals its soldier cells to make more antibody, swallow up the antigen or kill off cells containing the antigen.
In order for this response to work, however, the immune system has to know the antigen is there. That is where dendritic cells come in. Their job is to pick up an antigen and bring it to the lymph nodes where the immune cells live. The immune cells then realize something is wrong and travel through the body to destroy the antigen.
One approach to cancer immunotherapy involves loading dendritic cells with an antigen specific to the tumor — such as the virus found in glioblastoma — and injecting them into the patient. The idea is these dendritic cells will alert the immune system and the immune system will send its killer cells to attack the tumor.
This works to a degree, but a majority of the dendritic cells do not travel to the lymph nodes to signal an immune attack. This is where the tetanus booster comes in. If a patient has already received a tetanus shot, his body will recognize the tetanus antigen in the booster shot, and the immune system will attack the antigen. 
The tetanus booster also puts the immune system on alert. Both the act of fighting off the tetanus antigen and the creation of a protein called CCL3 help pull more dendritic cells to the lymph nodes. In essence, the body senses a threat and calls in its dendritic cell scouts to give it information on that threat. Injecting dendritic cells with the cancer antigen takes advantage of this high alert to warn the immune system about the cancer.
Dendritic Cell with AntigenIn both the human and mouse experiments, patients who received the tetanus booster saw twice as many dendritic cells migrate to lymph nodes as those who got placebo or lacked the ability to make CCL3 in the mouse trials.
What this shows is that both CCL3 and the natural response to the tetanus booster bring more dendritic cells to the lymph nodes, boost the immune attack against a tumor and improve the survival time for glioblastoma. 
Sampson says this research is in its early stages, but this small trial provides compelling enough evidence to move into more expansive trials and to investigate CCL3 even more. 
The tetanus shot method has two other major benefits as well. First, since millions of people get tetanus boosters every year without any problems, there is little worry that this treatment could be harmful, which would make clinical trials go more smoothly once this technology reaches that point.
Second is that this method has applications beyond glioblastoma. Several cancers have their own specific antigens not found in healthy cells, making them targets for immunotherapy. If the tetanus shot can boost the treatment for glioblastoma, it may also help the immune system fight off these other cancers.
While the tetanus shot may not be a cancer vaccine, this study shows that it may give the immune system an edge in battling the deadliest form of brain cancer.

— Daniel Lane

Daniel Lane covers science, engineering, medicine and the environment in North Carolina.

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