University of Florida researchers have launched a first-in-human clinical trial to test a novel immunotherapy treatment for children with an aggressive type of brain tumor.
The Phase 1 clinical trial is expected to enroll up to 18 children between 4 and 18 years old with pediatric high-grade gliomas that express a protein called CD70.
Brain and central nervous system tumors are the leading cause of cancer-related death in children, and pediatric high-grade gliomas are the most aggressive and lethal kind. These tumors grow rapidly, resist standard therapies and have few effective treatment options.
The new trial, led by Jianping Huang, M.D., Ph.D., and funded by the St. Baldrick’s Foundation, will test the safety and feasibility of a next-generation CAR T cell therapy called 8R-70CAR. Chimeric antigen receptor therapy, or CAR T cell therapy, takes a patient’s own immune cells, genetically modifies them outside the body and then reinfuses them.
Huang and her team previously identified CD70, a molecule involved in tumor progression and immune suppression, as a promising target for brain tumor therapy.
To overcome the challenges that CAR T cell therapies face in solid tumors, her team developed a platform that integrates a patented tumor positioning system. It works like a GPS navigation tool. CAR T cells are engineered to migrate toward a protein secreted by tumors.
“The result is 8R-70CAR, which homes in on the tumor, mounts a potent tumor attack and minimizes off-target toxicity,” said Huang, the principal investigator of the study and a professor in the Lillian S. Wells Department of Neurosurgery.
In preclinical models of glioblastoma, ovarian and pancreatic cancer, 8R-70CAR T cells showed complete tumor regression and long-term immune memory. These results led to FDA clearance of a clinical trial in adults with glioblastoma, which is underway at UF.
So far, three patients have been treated without dose-limiting toxicities on that trial, which has shown encouraging early efficacy, Huang said.
The pediatric trial, led by UF Health pediatric oncologist John Ligon, M.D., and conducted in collaboration with Eugene Hwang, M.D., at Children’s National Hospital, will build on that foundation as the pediatric trial.
Patients will receive the new therapy in addition to the standard of care chemotherapy and radiation. The clinical trial includes a comprehensive program to monitor how patients’ immune systems respond, helping guide future therapy improvements.
“We’re combining leading-edge science with a heartfelt commitment to improve the lives of children facing devastating brain cancers,” Huang said.
The studies have been supported by the Live Like Bella Pediatric Cancer Research Initiative (Florida Department of Health), U.S. Department of Defense, UF Health Cancer Center, McKnight Brain Institute and The Harris Rosen Foundation.
