By Ian Bennett | bennettian@ufl.edu
John Ligon, M.D., an assistant professor in the department of pediatrics in the University of Florida College of Medicine, has been awarded a $200,000 grant from Hyundai Hope on Wheels for a study to test new treatments for osteosarcoma.
Usually found in longer bones in the body, osteosarcoma is a type of bone cancer that affects children and adults and is commonly found in the arms and legs.
“Osteosarcoma is a particularly difficult cancer to treat and the treatments haven’t changed much in 40 years,” said Ligon, who is a member of the Cancer Center’s Cancer Therapeutics & Host Response research program. “Immunotherapy is something that allows us to use the body’s own immune system to attack cancer, but we don’t have good models for this specific cancer yet.”
One of the major challenges to developing new treatments is testing them for safety and effectiveness before taking them to human trials. Using tiny self-organized 3D tissue cultures, the Ligon lab plans to develop a new tumor model to test immunotherapies. Normally called organoids, these tiny models will be tumoroids and based on the tumor of the patient. Once the team develops an effective way to create these models, they will collaborate with other researchers to test new immunotherapies.
In earlier studies, the Ligon team found that osteosarcoma pulmonary metastases expressed multiple redundant immune checkpoint molecules. These molecules function as a system of checks and balances to enhance or inhibit immune responses. The team also found that tumor-associated macrophages and myeloid-derived suppressor cells can prevent immune cells from entering the tumor microenvironment. These two findings offer potential targets for immunotherapies, and the new models will serve as a way to test new treatments on these targets. The team hopes to test new treatments using RNA-nanoparticle vaccines.
The new project has three aims. First, the team will perform clinical trials with a 3D canine osteosarcoma tumoroid model. Once they validate the model in canines, they will create a pulmonary metastatic osteosarcoma tumoroid model for humans. After successfully creating these models, they will further study the impact of RNA nanoparticles on the immune response in combination with immune checkpoint inhibitors.
Ligon is collaborating with Elias Sayour, M.D., Ph.D., an associate professor of neurosurgery and pediatrics in UF’s College of Medicine, and W. Gregory Sawyer, Ph.D., a professor in the department of mechanical & aerospace engineering in the UF College of Engineering, who will provide expertise in 3D tumoroid and cancer engineering. Rowan Milner, Ph.D., a professor in the department of small animal clinical sciences in the UF College of Veterinary Medicine, will serve as a principal investigator for the canine osteosarcoma clinical trial. Elham Nasri, M.D., clinical assistant professor in the department of pathology, immunology and laboratory medicine in the UF College of Medicine, will assist with obtaining human tumor samples.
