Yesterday, an interesting study on brain cancer – funded in part by the National Brain Tumor Society – was published in the prominent scientific and medical journal, Nature. The encouraging results of the study even sent ripples through mainstream health media, including stories in top-tier outlets including the Wall Street Journal, NBC News, and CBS News.
What made the study so attention-grabbing was that it demonstrated a potential new method to enhance treatment and improve the survival of newly diagnosed glioblastoma multiforme (GBM) patients with a common shot.
The study presented data from a small, randomized, and blinded clinical trial led by researchers from Duke University. The trial compared the effectiveness of giving a tetanus booster – a common shot that most Americans receive at some point in their childhood – to patients prior to experimental immunotherapy, versus treating patients with the immunotherapy alone (following a placebo of shot).
The results showed that the 6 patients who received the tetanus booster prior to the immunotherapy lived longer than the 6 who received only the immunotherapy. Three of the patients who received the tetanus shot survived past the time end of the trial (~40 months), compared to an 18.5 month median in the control group. According to a press release, one patient from the tetanus shot group is still alive 8 years after receiving the treatment, with no sign of tumor re-growth.
What the researchers from Duke – led by Drs. John Sampson, who earlier this year participated in a Q&A for this blog on immunotherapy, and Duane Mitchell – believe they have discovered is that the tetanus shot “primes” the patients’ immune system to enhance the effect of the immunotherapy.
The immunotherapy the researchers are exploring is called a “dendritic cell vaccine.” Dendritic cells are cells within the human body that work to train the immune system to attack pathogens (viruses, bacteria, fungus, and other foreign invaders) in the body. Dendritic cells can be grown in the lab by extracting a patient’s own blood cells and then using enrichment techniques to produce more of the dendritic cells. Once researchers have newly developed dendritic cells, they can “load” them with a “viral antigen” that will tell the body’s immune system to seek out and destroy other cells infected by a specific, corresponding pathogen. These trained dendritic cells are then injected back into the patient and travel to lymph nodes, where they rally the body’s immune system to go fight the pathogen.
In this case, the pathogen is a strain of a virus called the cytomegalovirus, or CMV. Earlier discoveries had found that many GBM tumors contain CMV, but not healthy brain tissue. So the researcher’s dendritic cell vaccine carries an antigen that causes the immune system to recognize and attack the CMV-infected cells – which also happen to be the tumor cells.
This dendritic cell vaccine has been under testing on its own for GBM patients, and shown some promising early results in those trials, but researchers were looking to find ways to make it even more effective. Using animal models to track how the immunotherapy worked once in the body, they were able to surmise that given a “boost” (a tetanus shot is often also referred to as a “booster shot”) the vaccine could be even more powerful. Subsequently, testing began on if a tetanus shot could put the immune system on high alert before administering the dendritic cell vaccine, thus paving the way for a stronger response against the CMV pathogen once the antigen arrives in the lymph nodes.
This study is an encouraging development in brain tumor immunotherapy, and potentially provides an example for how to improve the effectiveness of these emerging treatments that could not only be applied to GBM, but other tumor types, as well.
However, it is important to keep in perspective the size of the study and that these results have not been confirmed. The researchers are currently pursuing further, large-scale confirmatory studies that are needed before this treatment approach can be validated for use in the larger patient population.
National Brain Tumor Society looks forward to following this approach as it moves into larger trails.