NIH-Funded Study Suggests Novel Strategy to Improve Vaccine Efficacy in the Treatment of Glioblastoma
Although dendritic cell–based immunotherapy has shown limited promise in the treatment of patients with advanced cancers, including glioblastoma, the factors dictating dendritic cell–based vaccine efficacy have been poorly understood. Now, a clinical trial funded by the National Institutes of Health of patients with glioblastoma has found that preconditioning the vaccine site with a potent recall antigen, such as tetanus/diphtheria (Td) toxoid can significantly improve the lymph node homing and efficacy of tumor antigen–specific dendritic cells. The researchers’ clinical studies and corroborating investigations in mice suggest that preconditioning with a potent recall antigen may represent a viable strategy to improve antitumor immunotherapy. The study is published in Nature.
Study Methodology
The investigators randomly assigned patients with glioblastoma to preconditioning with either mature dendritic cells or Td unilaterally before bilateral vaccination with dendritic cells pulsed with Cytomegalovirus phosphoprotein 65 (pp65) RNA. The researchers’ investigations and studies from other laboratories have shown that pp65 is expressed in more than 90% of glioblastoma specimens, but not in surrounding normal brain tissue, providing an opportunity for the researchers to subvert this viral protein as a tumor-specific target.
Study Findings
The study results showed that administering a tetanus booster before giving the vaccine increased dendritic cell migration to lymph nodes and also had a significant effect on clinical outcomes. The patients who received the tetanus booster lived more than 36.6 months after their diagnosis compared to an average survival time of 18.5 months in patients who received dendritic cells alone.
Next, the researchers used a mouse model to determine how the tetanus booster increased dendritic cell migration to the lymph nodes and found that the preconditioning also enhanced bilateral dendritic cell migration and suppressed tumor growth in a manner dependent on the chemokine CCL3.
“We did not expect that enhancing dendritic cell migration would be associated with such a dramatic improvement in clinical outcomes in our patients,” said Duane A. Mitchell, MD, PhD, Director of the Brain Tumor Immunotherapy Program at the University of Florida in Gainesville, and co-lead author of the study, in a statement. “Dendritic cell vaccines targeting glioblastoma can be very effective by enhancing migration of dendritic cells. We now understand how we may improve outcomes for patients receiving this type of therapy.”
“Our clinical studies and corroborating investigations in mice suggest that preconditioning with a potent recall antigen may represent a viable strategy to improve antitumor immunotherapy,” concluded the researchers.
Dr. Mitchell and John H. Sampson, MD, PhD, of Duke University Medical Center, are the corresponding authors of the Nature article.
Funding for this study was provided by grants from the National Institute of Neurological Disorders and Stroke and the National Cancer Institute.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
