A UF researcher has launched a new clinical trial to test a novel UF-developed mRNA lipid nanoparticle (RNA-LP) that is designed to reprogram the immune system in two pediatric cancers.
John Ligon, M.D., an assistant professor in the Department of Pediatrics, is leading the trial that is investigating the safety and immune system response from RNA-LP in children with recurrent high-grade glioma, a brain tumor, and recurrent osteosarcoma, a bone cancer.
The RNA-LP technology is the same that was used in a first-ever human clinical trial of four adult patients at UF, where it quickly reprogrammed the immune system to attack glioblastoma. The RNA-LP uses an iteration of mRNA technology and lipid nanoparticles, similar to COVID-19 vaccines. A patient’s own tumor cells are used to create a personalized mRNA cancer therapeutic, which works through a newly engineered complex delivery mechanism.
UF researchers showed the feasibility of this approach in pet dog patients suffering from naturally occurring brain tumors whose owners approved of their participation, as they had no other treatment options, as well as in preclinical mouse models.
“This is a novel ‘basket’ trial that will test this new mRNA technology in multiple pediatric cancers,” said Ligon, a member of the UF Health Cancer Center’s Immuno-Oncology and Microbiome research program.
Phase 1 of this trial will evaluate the feasibility of making the product and the safety of the product in patients. Phase 2 of the trial will assess event-free survival in patients.
“Our goal is to test whether immune cells in patients receiving the RNA-LP become activated in both peripheral blood and in the tumor,” Ligon said. “We will also assess the overall survival rate in patients receiving the treatment.”
The trial is expected to enroll about 36 patients. Patients ages 3 to 25 with recurrent or progressive pediatric high-glioma or ages 3 to 39 with osteosarcoma that has recurred to the lungs or that is not treatable with surgery are eligible to enroll.
Gliomas are tumors that start in glial cells, the supporting cells of the brain. About half of all brain and spinal cord tumors in children are gliomas, and these tumors are the second most common cancers in children, after leukemia, according to the American Cancer Society.
Osteosarcoma is a rare cancer that starts in the bones. Treatment options are typically limited when it spreads to distant parts of the body, such as the lungs. The American Cancer Society estimates the five-year relative survival rate in those cases is less than 25%.
Ligon aims to add additional arms to the clinical trial to use the RNA-LP technology to generate a personalized immunotherapy for other types of difficult-to-treat, relapsed pediatric cancers in the future.
This trial is an outgrowth from a challenge grant from Stop Children’s Cancer, challenging Ligon’s team to open a clinical trial for osteosarcoma at UF.
“This challenge grant enabled us to develop this novel cancer therapeutic, which has now been extended to multiple types of tumors, including osteosarcoma and pediatric high-grade glioma,” Ligon said.
Support for the trial also came from the V Foundation for Cancer Research, the National Pediatric Cancer Foundation, Alex’s Lemonade Stand Foundation and the National Cancer Institute.
