Two novel immune approaches developed at the Preston Robert Tisch Brain Tumor Center to treat deadly brain tumors have received nearly $7 million in funding under the National Cancer Institute’s prestigious Outstanding Investigator Award program.
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. 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 lethal glioblastoma tumors -- that are already showing promise in early clinical trials.
New studies will combine each of the immunotherapies with a class of drugs called checkpoint inhibitors, which work to awaken the body’s immune system to attack cancer cells.
“This is extremely important support for our work, and we are excited to move forward with the studies,” Bigner said.
Bigner said animal studies are already underway, and clinical trials could launch within two years with the new funding. The pre-clinical work will focus on determining how well the checkpoint inhibitors provide a one-two punch 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 affects of the immunotherapies,” Bigner said.
Duke’s poliovirus therapy is currently in a phase 1 study and was the subject of a lengthy report on 60 Minutes in March. 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,” Bigner said.
In addition to Bigner, the research team includes Annick Desjardins, M.D.; Xuhui Bao; Vidya Chandramohan, Ph.D.; Allan H. Friedman, M.D.; Henry S. Friedman, M.D.; Matthias Gromeier, M.D; Smita Nair, Ph.D.; John H. Sampson, M.D., Ph.D.; and Gordana Vlahovic, M.D.