By: Tara Haelle
From: forbes.com
It’s one of the oldest, most effective, and most familiar vaccines – and it just became another tool in our arsenal to fight cancer. In a small trial involving 12 patients, researchers recently used the tetanus vaccine – yes, the same vaccine you get when you end up in the ER after stepping on a rusty nail – to “prime” the immune systems of patients with brain tumors. Then they administered immunotherapy using a new kind of cellular cancer vaccine that trains the immune system to fight the tumor without affecting nearby healthy cells.
Using this one-two punch of a highly effective traditional vaccine and an innovative cancer vaccine, patients with glioblastoma, the same cancer that killed Sen. Edward Kennedy in 2009, lived from 4 to 8 more years after their treatment, compared to 11 more months in the patients who received the immunotherapy with a placebo injection instead of the tetanus booster. One patient is still alive eight years later, according to the study published March 11 in Nature.
To understand how the tetanus vaccine helped and what is so special about this new cancer vaccine, it’s first necessary to understand how cancer immunotherapy works. For most of the past six decades, the standard of care in treating cancer has been surgical removal of tumors when possible, followed by radiation and chemotherapy. Those methods remain the first-line options to treat a cancer, but if they aren’t enough, the next step is increasingly some form of immunotherapy, which harnesses the power of the best disease-fighting mechanism we know of – our own immune systems.
But cancer typically keeps an upper hand by suppressing the immune system, so the system needs specific instructions to fight cancer or a boost, or both. Specific instructions can be delivered with cellular “vaccines.” Traditional vaccines deliver inactivated viruses or bacteria (or pieces of them) to healthy individuals, and these antigens (the intruder the immune cells recognize as the enemy) stimulate their immune system to create antibodies for those pathogens. Cancer vaccines, however, provide marching orders for the immune system to target only the cancer cells — and no other cells — in someone who is already ill. They can only do this, however, if they’re trained to know the difference, and much of today’s cancer research focuses on identifying some characteristic of cancerous cells, usually a mutation of some sort, that differs from a tissue’s normal, healthy cells.
The two major challenges of immunotherapy are identifying what to target in each different type of cancer cell and then getting the immune system to cooperate when the cancer has so severely weakened it. This small trial tried something new to overcome both those challenges. First, instead of targeting a mutation in the brain tumor cells, they targeted exactly the sort of beast the human immune system was naturally designed to fight: a virus. Nearly all people have been exposed to cytomegalovirus, a relatively benign member of the herpesvirus family that rarely causes illness but remains dormant in the bodies of those exposed to it. It turns out that cytomegalovirus reactivates in glioblastoma cells, probably because of the immunosuppressive power of the tumor cells.
“That’s a huge advantage because the cytomegalovirus appears within the tumor cells and not the surrounding normal, healthy brain tissue or anywhere else in the body, so it’s a very good potential target to train the immune system to fight what’s in the tumor and only that,” said study co-author Kristen Batich, an M.D. and Ph.D. candidate at Duke University Medical Center.
So Batich and her colleagues collected white blood cells from 12 glioblastoma patients and developed a method to grow dendritic cells, the immune cells whose job is to collect antigens from a pathogen and present these to T cells to train them to go after the pathogen. (Imagine collecting a piece of a suspect’s clothing – the antigen – and presenting it to a police dog to train him to sniff out the suspect, except T cells would go after and kill the suspect.) Then the researchers filled these dendritic cells with cytomegalovirus antigens and injected them into the patients. Ideally, the dendritic cells would meet up with T cells and show them the antigens, thereby training them to go out and attack only the cells containing cytomegalovirus.
But here is where immunotherapy might run the risk of failure.
“We had known from other studies using dendritic cell vaccines that once you inject the cellular vaccine into the patient, only a limited amount of the cells get to the lymph nodes,” Batich said. “That’s where they need to go to train the immune cells to go off and fight the tumor, so it’s critical that these dendritic cells get there.”
That’s where the tetanus vaccine comes in. In the six patients who received the tetanus shot the day before their immunotherapy, the immune system mounted a typical response to the vaccine, ramping up production of tetanus antibodies. But more importantly, the tetanus vaccine also acted like Paul Revere, shouting out warnings that more intruders may be on the way. With the immune system now on the lookout, the dendritic cells were immediately ushered to T cell headquarters when injected.
“What we think is going on is that the tetanus booster vaccine facilitates that migration pathway to the lymph nodes and allows the [cellular] vaccine to work to a greater degree,” Batich said. “We think that if you reach a certain threshold of dendritic cells getting to the lymph nodes, it can make a much bigger splash in terms of the immune response.”
Although the trial is small, the dramatic difference in additional survival time among those who first received the tetanus vaccine implies the strategy worked.
The use of dendritic cell vaccines is not new to cancer immunotherapy. A great deal of research, especially with advanced melanoma, has shown their effectiveness in killing cancer cells when trained what to target. But using dendritic cells to target an actual virus instead of cellular mutations is new. By targeting cytomegalovirus – present only in the tumor cells – healthy cells don’t get caught in the crossfire. Using the tetanus vaccine like a warning siren to increase the dendritic cells’ success is new as well and might have applications well beyond glioblastoma treatment.
“It certainly has implications to be brought into other very aggressive cancers where you have cancer-specific targets because tetanus is so good at creating an inflammatory response and waking up the immune system,” Batich said. “It could potentially do it to any other number of targets that you’re trying to fight in a tumor.” In fact, she said, tetanus creates such a strong, high-alert response that it may even work beyond cancer treatments, potentially supporting therapies in treating, for example, chronic viral infections. Yet this study was still very small and focused only on glioblastoma, Batich cautioned, so they plan to do a larger follow-up study with more patients. Glioblastoma comprise approximately 17 percent of all primary brain tumors, according to the American Brain Tumor Association.
More research will tell us whether the tetanus booster can do more than prevent the awful bacterial infection living in the soil and on rusty nails. It may also boost the body’s ability to fight cancer.
Barbara Jacoby is an award winning blogger that has contributed her writings to multiple online publications that have touched readers worldwide.