Lymphocyte activation gene-3 (LAG-3) has emerged as one of the most promising and potential targets in cancer therapy. Creative Biolabs shares new advances in structural studies of the LAG-3 molecule, providing researchers with new insights for future basic and applied studies.
A major function of LAG-3 is to negatively regulate major histocompatibility complex class II (MHCII)-mediated T cell activation. In addition to MHCII, multiple other ligands for LAG-3 have been identified, namely fibrinogen-like protein 1 (FGL1), LSECtin, galectin 3, and α-synuclein. Although LAG3 is expressed in T cells in a TCR signaling-dependent manner, it is also present and active on immune cells lacking TCR expression.
Thus, this suggests that LAG-3 biology is relatively complex and that LAG-3 may have multiple functions.
Therefore, an in-depth study of the molecular structure, epitopes and functions of LAG-3 will
Researchers co-crystallized the LAG-3 D1-D4 domains with a single-chain variable fragment (scFv) of an F7 antagonist to characterize the structure of the LAG-3 extracellular domain.
Fig. 1 Comparison of the crystal structures of mouse LAG3 dimer including domains D1 and D2 (left), and human LAG3 dimer including domains D1–D4 (right) from the LAG3 complex structure with F7 scFv.1
Many biopharmaceutical companies are currently investing in and developing LAG-3 programs, and there are currently at least one hundred clinical trials related to LAG-3 in clinical trials. To date, at least 20 drugs have been developed that target LAG-3. These include anti-LAG-3 blocking antibodies, as well as antagonistic bispecific antibodies.
Structural studies of LAG-3 have not only provided insights into the biology of LAG-3, but have also laid the foundation for the evaluation of agonist and antagonist antibodies against LAG-3 and the rational development of small-molecule inhibitors targeting LAG3-ligand interactions.
Creative Biolabs learns and continues to explore a number of important recent studies, which assist us in providing LAG-3 related services to our customers.
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