On December 16, 2024 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a clinical-stage biotechnology company developing novel LAG-3 immunotherapiesfor cancer and autoimmune disease, reported new findings published in Science Immunology that resolve how human lymphocyte activation gene 3 (LAG-3) binds to its main ligand MHC Class II (MHC-II), also known as HLA Class II (HLA-II) in humans (Press release, Immutep, DEC 16, 2024, View Source [SID1234649116]). The publication is the first to show the crystal structure of a human LAG3/HLA-II complex and provides a better foundation for development of blocking LAG-3 therapeutics, including Immutep’s anti-LAG-3 small molecule program.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
Under the oversight of Professor Jamie Rossjohn FAA FRS, at Monash University’s Biomedicine Discovery Institute (BDI), and in collaboration with Immutep, this breakthrough is an exemplar of the importance of industry-academia alliances. The LAG-3 immune control mechanism is the exclusive focus of Immutep across both cancer and autoimmunity and a clinically validated target of deep interest throughout the academic, medical, and industry sectors.
Dr. Jan Petersen, first author of the study,said: "The way the PD-1 and CTLA-4 immune checkpoint molecules bind to their respective ligands has been resolved for many years. However, the resolution of the interface between another important checkpoint molecule, LAG-3, and its main ligands, HLA-II molecules, has remained elusive. Solved using data collected at the Australian Synchrotron, a structure of a LAG-3/HLA-II complex provides a structural foundation to harness rationally for future development of antibodies and small molecule therapeutics designed to block LAG-3 activity."
Dr. Frédéric Triebel, Immutep’s CSO, added: "It is thrilling to be able to see and analyze the interactions taking place at the interface between the soluble homodimeric LAG-3 protein and its main ligand. We now better understand how efti uniquely acts as an MHC-II agonist by preferentially binding to a subset of MHC-II molecules clustered in lipid raft microdomains on the surface of antigen-presenting cells. 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 antiLAG-3 small molecule program."
The Crystal Structure of the Human LAG-3–HLA-DR1–Peptide Complex publication details how LAG-3 engages two HLA-II molecules (see Figure 1). The data in the publication supports efti’s (soluble LAG-3) preferential binding to a subset of MHC-II molecules on antigen-presenting cells leading to their activation