A tetanus shot may boost the efficacy of a vaccine used to treat lethal brain tumours, dramatically improving patient survival, researchers, including one of Indian-origin, have found.
Researchers show how the tetanus pre-conditioning technique works, providing a roadmap for enhancing dendritic cell immunotherapies that have shown promise treating the most lethal form of brain cancer.
"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, chief of the Division of Neurosurgery at Duke University Medical Centre.
The researchers built the study on earlier findings that glioblastoma tumours harbour a strain of cytomegalovirus (CMV) that is not present in the surrounding brain tissue, creating a natural target for an immune therapy.
One such targeted approach uses dendritic cells, which train the immune system to respond to specific pathogens. The team developed a process to extract white blood cells, coax the growth of dendritic cells and load them with the 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 tumour.
This immunotherapy worked well, but researchers, including Smita K Nair from Duke, looked for a way to prime the immune system to be on high alert prior to the infusion of dendritic cells.
They used a shot of tetanus/diphtheria toxoid - which is widely available and safe as a clinically approved vaccine - to incite the troops of lymphocytes in the lymph nodes.
In a small human study, they enrolled 12 brain tumour patients, with half randomly assigned to receive a tetanus booster and the other half a placebo injection.
The next day, patients in both groups were then given the dendritic cell immunotherapy. Researchers did not know which therapies the patients received.
Patients randomised to get a tetanus shot showed a significant increase in survival from the time of pre-conditioning compared to patients receiving just the dendritic cell therapy, with half living from 51 to 101 months, compared to 11.6 months for the comparison group.
One patient from the tetanus group continues to have no tumour growth and is still alive at eight years after the treatment, researchers said.
"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," said co-lead and co-corresponding author, Duane A Mitchell, currently director of the University of Florida brain tumour immunotherapy programme.
The research was published in the journal Nature.
