A tetanus booster shot was found to enhance the effect of vaccine therapy for brain tumors, improving patient survival, according to a small, randomized, blinded clinical trial, the results of which were recently published in Nature. The authors, from Duke University Cancer Institute in Durham, North Carolina, detailed what they call “tetanus pre-conditioning” and offered a roadmap for how to enhance dendritic cell immunotherapies that show promise for treating glioblastoma.
“Patients with glioblastoma usually survive for little more than one year. However, in patients who received the immunotherapy, half lived nearly five years or longer from their diagnosis, so the findings are promising and significant,” said senior author John Sampson, MD, PhD, chief of the division of neurosurgery at Duke University Medical Center, in a prepared statement.
The new study builds on earlier research that glioblastoma tumors contain a strain of cytomegalovirus (CMV) that is not found in surrounding brain tissue—making it a good target for immune therapy such as that using dendritic cells. Duke researchers extracted white blood cells, then coaxed the growth of dendritic cells and loaded them with viral antigens. “Armed with these marching orders, the dendritic cells are injected back into the cancer patients, where they head to the lymph nodes and signal the immune fighters to search and attack the CMV-laden tumor,” explained a press release describing the study.
Finding that immunotherapy worked well, the research team then investigated ways to prime the immune system to prepare for the injection of the dendritic cells. They enrolled 12 patients with brain tumors in a small study and randomly assigned half to get a tetanus booster shot, and the other half a placebo shot. The following day, both groups of participants were injected with dendritic cell immunotherapy.
Those who received a tetanus shot had a significant increase in survival compared with patients who received dendritic cell therapy alone. Half of those who got the shot lived from 51 to 101 months, compared with 11.6 months in the comparison group. Also, one patient who received a tetanus shot still has no tumor growth 8 years after treatment.
“These findings have potential relevance for improving dendritic cell vaccines not only for patients with glioblastoma, but also in the immunologic targeting of other cancers,” co-lead and co-corresponding author, Duane A. Mitchell, MD, PhD, director of the University of Florida brain tumor immunotherapy program, said in a prepared statement. “We are obviously pursuing larger-scale confirmatory studies, but are very encouraged by these data and the future applicability.”