Francesca Tomasi received her B.A. from the University of Chicago and is now a microbiologist.
Cytomegalovirus (CMV) is a member of the herpesvirus family and infects many people yet rarely causes symptoms. In fact, the only people for whom this large virus poses a cause for concern are individuals who are pregnant or who have a weakened immune system. Infection with CMV is lifelong for everybody, but the virus remains dormant in healthy people. While there is no cure for CMV, drugs can help treat immunocompromised patients such as individuals undergoing cancer treatment who may be infected with the virus.
Recently, researchers found a significant association between CMV and glioblastoma multiforme. Glioblastomas are the most common and aggressive brain tumor, accounting for about 15% of all cases. After initial diagnosis, survival is typically less than 15 months, with fewer than 5% of people surviving more than 5 years. Without treatment, survival is about 3 months. This wasn’t the first time a virus has been connected to cancer, and it certainly will not be the last. In 2002, a neurosurgeon named Charles Cobbs noticed that a high percentage of glioblastoma tumors he examined were infected with CMV. Furthermore, the virus did not reside in healthy tissue surrounding these tumors. In 2013, a study performed in Sweden found that different levels of CMV infection were correlated with survival: a lower viral count correlated with a longer survival. Though this link has not been proved causally, this and similar studies do suggest a CMV contribution to the progression of glioblastoma.
Researchers are still studying the relationship between cytomegalovirus and glioblastoma. At Duke, a new immunotherapy targeted against CMV antigens (substances produced by pathogens that trigger an immune response) has shown promising results. Even more exciting is the success of a supplement to this immunotherapy many people may find surprising: a tetanus shot.
Since CMV is often present in tumors but not in surrounding healthy tissue, the virus was chosen as a target for immune therapy: attack the virus, and you’re attacking the tumor. Dendritic cells are members of the immune system responsible for responding to specific pathogens. The research team at Duke therefore developed a process in the lab to extract white blood cells (immune cells), induce the growth of dendritic cells, and challenge them with CMV antigens. These dendritic cells were then injected back into their humans, armed and ready to fight any hint of CMV. This specificity led the immune system straight to glioblastoma cells, right where the virus was lurking.
Alone, this targeted immunotherapy showed promising results. But the Duke team wanted to improve prognoses even more, so they set out to find a way to put the immune system on red alert before re-injecting dendritic cells back into the body. That way, they hoped to strengthen the immune response in general and therefore against CMV. So they chose a widely available and safe vaccine.
In a recently published clinical study, 12 brain tumor patients were randomly assigned to receive a tetanus booster shot or a placebo shot. Both groups were then given the dendritic cell immunotherapy.
Patients who received the tetanus shot showed a significant increase in survival compared to patients receiving only the dendritic cell therapy; 3 out of 6 patients lived 51 to 101 months, compared to 11.6 months in the other group. One patient who received the tetanus shot has been tumor-free for eight years.
Larger-scale studies will give a more accurate estimate of the therapy’s success rate, but this small study sheds a promising light on immunotherapy and vaccine supplementation. Based on animal studies, the Duke team thinks immune cells armed against different antigens – in this case, tetanus and CMV – work together to amp up the capacity for dendritic cells to localize to a site of infection and exert their protective effects.