The Preston Robert Tisch Brain Tumor Center at Duke has received nearly $7 million in funding under the National Cancer Institute’s (NCI) Outstanding Investigator Award program for work on two novel immunotherapy approaches to treat brain tumors. The award recognizes the work of principal investigator Darell Bigner, MD, PhD, Director of the Preston Robert Tisch Brain Tumor Center at the Duke Cancer Institute. Dr. Bigner and the other 42 recipients nationwide were selected for “providing significant contributions toward understanding cancer and developing applications that may lead to a breakthrough in biomedical, behavioral, or clinical cancer research,” according to the NCI.
The funding supports additional animal and human studies for two separate immunotherapies—one using a modified poliovirus, and another using a bacterial immunotoxin to attack glioblastoma tumors—that are already showing promise in early clinical trials. New studies will combine each of the immunotherapies with a checkpoint inhibitor.
“This is extremely important support for our work, and we are excited to move forward with the studies,” Dr. Bigner said.
Preclinical Studies Underway
Dr. Bigner said animal studies are already underway, and clinical trials could launch within 2 years with the new funding. The preclinical work will focus on determining how well the checkpoint inhibitors provide a response when combined with the immunotherapies. The early studies will also identify which checkpoint inhibitors work best in the combination approach.
“We’ve actually begun the animal studies and are learning that the checkpoint inhibitors do exactly as hoped—they accentuate the effects of the immunotherapies,” Dr. Bigner said.
Duke’s poliovirus therapy is currently in a phase I study. The therapy uses deactivated poliovirus, which is predisposed to selectively attach to tumor cells and not healthy cells. After surgically injecting the modified virus into the brain tumor, the immune system goes to work, attacking the virus-infused tumor.
The second brain tumor therapy uses a toxin from the Pseudomonas bacterium and an immune system single fragment chain antibody, which are paired in a therapy that works in much the same way as the poliovirus approach. The antibody component selectively binds to brain tumor cells, while the toxin then kills those cells.
“We believe that by adding the checkpoint inhibitors, we will get even better results than we have seen using the poliovirus and the immunotoxin alone,” Dr. Bigner said.
In addition to Dr. Bigner, the research team includes Annick Desjardins, MD; Xuhui Bao; Vidya Chandramohan, PhD; Allan H. Friedman, MD; Henry S. Friedman, MD; Matthias Gromeier, MD; Smita Nair, PhD; John H. Sampson, MD, PhD; and Gordana Vlahovic, MD. ■