Scientists from Children’s Hospital of Philadelphia (CHOP) and Stanford University have decoded the molecular structure of TRACeR-I, an innovative protein platform designed to reprogram immune responses. The discovery, published in Nature Biotechnology, is a major step forward in optimizing this platform for developing cancer immunotherapies.
TRACeR-I holds promise for transforming cancer treatment by either modifying immune cells directly or creating proteins that enhance their ability to identify and attack cancer cells. Immunotherapy, a key tool in treating cancer, autoimmune diseases, and viral infections, relies on precision targeting of diseased cells. While monoclonal antibodies currently play a major role by targeting antigens on cell surfaces, their scope is limited by the sparse presence of unique antigens on diseased cells.
TRACeR-I aims to overcome this limitation by focusing on peptides displayed on the major histocompatibility complex (MHC), which showcases fragments of cancer or viral proteins on cell surfaces. However, with over 30,000 MHC-I protein variants in humans, developing treatments that recognize peptides across diverse patient populations has proven challenging.
Stanford researchers addressed this hurdle by developing TRACeRs, platforms capable of recognizing multiple versions of MHC proteins. These platforms act as “master keys,” targeting disease-associated peptides while sparing healthy cells.
“Our TRACeR-I and TRACeR-II platforms overcome historical barriers in MHC-targeting therapies by offering high specificity, broad compatibility with antigens, and simplified development,” explained Dr.Possu Huang, senior author and assistant professor of bioengineering at Stanford University.
To refine TRACeR-I, CHOP researchers used X-ray crystallography to map its structure, revealing how it attaches to conserved regions of the MHC-I complex while maintaining the ability to recognize disease-associated peptides.
“We’ve shown how TRACeR-I’s unique binding mechanism allows it to identify surface markers of cancer cells,” said Dr. Nikolaos Sgourakis, associate professor at CHOP. “This collaborative effort has helped bring the therapeutic potential of the Huang lab’s designs closer to reality.”
As reported by medicalxpress, the breakthrough offers hope for the development of precise, versatile immunotherapies that could revolutionize cancer treatment and other immune-based therapies.