Researchers at the UNC School of Medicine and UNC Lineberger Comprehensive Cancer Center are zeroing in on less toxic and more targeted strategies to combat Ewing sarcoma, an aggressive and rare pediatric cancer that develops in the bones and soft tissues.
In a new study, researchers have identified a promising target for Ewing sarcoma: a protein termed LINGO-1. A paper, published in the Journal of Clinical Investigation, detailed their findings and demonstrated how this protein can serve as a unique tumor-targeting drug delivery antenna to suppress Ewing sarcoma tumor growth.
"We hope these findings will pave the way for the development of more effective targeted therapies and ultimately improve outcomes for patients with this devastating disease," said Pengda Liu, PhD, an associate professor of biochemistry and biophysics and member of UNC Lineberger Comprehensive Cancer Center.
Pengda Liu, PhD
Chemotherapy - though effective for many cancers - can cause many side effects and irreparably harm healthy cells in the body. To better improve patient outcomes, researchers are focused on creating special molecules called antibody-drug conjugates (ADCs).
The special molecule is made up of two components: a monoclonal antibody (lab-created immune cells) and an anticancer drug. The antibody plays the role of the navigator, while the anticancer drug carries out the attack once inside of cancer cells.
But the approach only works when researchers have a specific tumor target in mind to direct the ADC's killer response. The team focused on LINGO-1, a protein Liu's team had confirmed on the surface of Ewing sarcoma cells.
Overall, their study looked at different kinds of ADCs that target the LINGO-1 protein. They found that opicinumab-MMAE has the most promise, as it showed no overt toxicity and was able to suppress tumor growth in immunocompromised preclinical models with Ewing sarcoma.
Liu and his team are planning additional studies to evaluate the clinical potential of other LINGO-1-specific ADCs in preclinical models and patients with typical immune function. They are also interested in investigating immunotherapies, including CAR-T cells, that are designed to recognize and attack the LINGO-1 protein.
