Australian-led research is opening up new ways for immunotherapy to better target cancer.
Cancer immunotherapy has revolutionized the treatment of patients, by harnessing the body’s own immune system to destroy cancer cells.
Normally, several molecules restrict the ability of T cells to attack cancer cells and the development of approaches to limit this restrictive effect may lead to greater efficacy of cancer immunotherapy.
Research published in Scientific immunology has determined the structure of how an inhibitory molecule, LAG3, interacts with its primary ligand and provides a new approach aimed at improving the effectiveness of immunotherapy for certain forms of cancer.
The publication is the first to show the crystal structure of a human LAG-3/HLA-II complex and provides a better basis for the development of LAG-3 blocking therapies.
Led by Professor Jamie Rossjohn from the Biomedicine Discovery Institute (BDI) at Monash University, Melbourne, Australia, in collaboration with Immutep, this research resolves how the human LAG-3 receptor binds to HLA II molecules.
First author Dr Jan Petersen said: “How the immune checkpoint molecules PD-1 and CTLA-4 bind to their respective ligands has been resolved for many years.
“However, resolution of the interface between another important checkpoint molecule, LAG-3, and its main ligands, HLA-II molecules, remains elusive.
“Solved using data collected at the Australian Synchrotron, a structure of a LAG-3/HLA-II complex provides a structural basis to rationally leverage the future development of antibodies and small molecule therapies designed to block LAG-3 activity.”
Dr Frédéric Triebel, CSO of Immutep, added: “These findings add to the strong foundation of our work with Professor Rossjohn and his team to develop a deeper understanding of the structure and function of the LAG-3 immune control mechanism. , particularly as it relates to our anti-LAG-3 small molecule program.”