Cancer immunotherapy has transformed patient treatment by utilizing the body’s immune system to eliminate cancer cells. Generally, various molecules inhibit T cells from effectively targeting these cells, and finding methods to reduce this inhibition can enhance the success of immunotherapy. Recent research has unveiled the structure of the inhibitory molecule LAG3 and its interaction with its primary ligand, paving the way for new, targeted strategies to enhance immunotherapy for specific cancer types.
Australian-led research is unlocking new ways for immunotherapy to better target cancer.
Cancer immunotherapy has changed the landscape of treatment for patients by leveraging the body’s immune defenses to attack cancer cells.
Typically, multiple molecules hinder T cells from properly targeting cancer, and developing techniques to minimize this hindrance could significantly boost the efficacy of cancer immunotherapy.
A study published in Science Immunology has revealed how the inhibitory molecule LAG3 works with its key ligand, offering new, focused approaches to enhance immunotherapy’s effectiveness for certain cancers.
This publication marks the first time the crystal structure of a human LAG-3/HLA-II complex has been showcased, establishing a stronger base for creating therapies that block LAG-3.
The research led by Professor Jamie Rossjohn at Monash University’s Biomedicine Discovery Institute (BDI) in Melbourne, in partnership with Immutep, clarifies how the human LAG-3 receptor connects with HLA II molecules.
Dr. Jan Petersen, the lead author, stated: “For many years, the ways PD-1 and CTLA-4 immune checkpoint molecules interact with their ligands have been well understood.
“However, understanding the interaction between the important checkpoint molecule LAG-3 and its main ligands, HLA-II molecules, has been more challenging.
“The structure of the LAG-3/HLA-II complex, resolved with data from the Australian Synchrotron, provides a solid basis for the future design of antibodies and small molecule drugs aimed at inhibiting LAG-3 activity.”
Dr. Frédéric Triebel, Immutep’s Chief Scientific Officer, remarked: “These discoveries enhance our collaborative efforts with Professor Rossjohn and his team to gain a comprehensive understanding of the LAG-3 immune regulatory mechanism, particularly in relation to our anti-LAG-3 small molecule initiatives.”
