LAG3 Antibodies

Structure of LAG3

LAG3 is a transmembrane immune checkpoint protein with a molecular weight of approximately 45-50 kDa, and its precise molecular weight varies slightly depending on the degree of glycosylation modification.

LAG3 is composed of 498 amino acids, and its extracellular region contains four immunoglobulin-like (Ig-like) domains (D1-D4), among which the D1 domain is responsible for binding to MHC class II molecules. The transmembrane region of this protein anchors it to the cell membrane, while the intracellular segment contains a unique "KIEELE" signaling motif that mediates immunosuppressive function. LAG3 plays a key role in tumor immune escape and autoimmune diseases by regulating the T-cell activation threshold. Its inhibitory function depends on the interaction with ligands (such as FGL1, Galectin-3, etc.), and this mechanism has become an important target for cancer immunotherapy.

Fig. 1 LAG3 biology on immune cells.¹

Key structural properties of LAG3:

• The extracellular region composed of Ig-like domains
• Transmembrane regions and intracellular signal motifs
• Ligand binding interface
• Disulfide bonds stabilize the structure
• Glycosylation modification site

Functions of LAG3

LAG3, as a key immune checkpoint molecule, mainly negatively regulates T cell activity to maintain immune homeostasis and also plays a significant role in tumor immune escape. Its multi-functionality is reflected in the following aspects:

The discovery of this gene provides a key target for the development of novel immune combination therapies (such as LAG3/PD-1 dual blocking), and the FDA's approval of anti-LAG3 monoclonal antibody in 2022 marks an important breakthrough in this field.

Applications of LAG3 and LAG3 Antibody in Literature

1. Shi, An, et al. "Immune checkpoint LAG3 and its ligand FGL1 in cancer." Frontiers in immunology 12 (2022): 785091. https://doi.org/10.3389/fimmu.2021.785091

The article indicates that the interaction between LAG3 and FGL1 inhibits the tumor immune microenvironment, and its domain (D1/D2 of LAG3 and FD of FGL1) mediates the function. LAG3 is enriched on the surface of lymphocytes, while FGL1 is expressed on the cell membrane of breast cancer cells. The co-expression of the two enhances PD-1-mediated immunosuppression. Antibodies targeting LAG3 (such as relatlimab) have been used for melanoma, while the high expression of FGL1/LAG3 leads to resistance in EGFR-TKI and PD-1 treatment. This review provides new ideas for anti-cancer strategies.

2. Graydon, Colin G., Shifa Mohideen, and Keith R. Fowke. "LAG3's enigmatic mechanism of action." Frontiers in immunology 11 (2021): 615317. https://doi.org/10.3389/fimmu.2020.615317

The article indicates that LAG3 is an important immune checkpoint, involved in tumors, infections and autoimmune diseases, but its mechanism of action remains unclear. This review explores the transcriptional and post-translational regulation of LAG3, ligand interactions (such as MHC-II and FGL1), and signaling mechanisms (unrelated to CD4). LAG3 mediates immunosuppression by inhibiting T cell activation and promoting depletion. Targeting LAG3 can enhance anti-tumor immunity, but its biological characteristics still require in-depth research.

3. Wu, Renzheng, et al. "LAG3 immune inhibitors: a novel strategy for melanoma treatment." Frontiers in Oncology 14 (2024): 1514578. https://doi.org/10.3389/fonc.2024.1514578

The article indicates that LAG3 inhibitors offer a new direction for the treatment of advanced melanoma. Although breakthroughs have been made in PD-1/CTLA-4 inhibitors, patients are prone to developing drug resistance. LAG3 promotes immune escape by inhibiting T cell function. Its inhibitors can restore T cell activity and work synergistically with existing immunotherapies. Targeting LAG3 is expected to overcome the problem of drug resistance and improve the therapeutic effect.

4. Solinas, Cinzia, et al. "LAG3: the biological processes that motivate targeting this immune checkpoint molecule in human cancer." Cancers 11.8 (2019): 1213. https://doi.org/10.3390/cancers11081213

The article indicates that LAG3, as an emerging immune checkpoint molecule, plays a key regulatory role in the tumor microenvironment. This article focuses on the expression characteristics of LAG3 in breast cancer and its clinical application prospects, including the progress of clinical trials of soluble LAG3 immunoglobulins and antagonists, providing new targets for tumor immunotherapy.

5. Ulase, Dita, et al. "LAG3 in gastric cancer: it's complicated." Journal of Cancer Research and Clinical Oncology 149.12 (2023): 10797-10811. https://doi.org/10.1007/s00432-023-04954-1

This study, through the analysis of 580 gastric cancer samples, found that the distribution difference of LAG3 positive cells between the tumor center and the invasion frontier significantly affects prognosis. In primary gastric cancer, the survival period of the LAG3 high-expression group (tumor center ≥21.45 cells /mm², invasion frontier ≥208.50 cells /mm²) was significantly prolonged. In the neoadjuvant therapy group, high expression of LAG3 in the tumor center (≥12.62 cells /mm²) was an independent prognostic factor. The results indicated that a high density of LAG3 was associated with a good prognosis.

Creative Biolabs: LAG3 Antibodies for Research

Creative Biolabs specializes in the production of high-quality LAG3 antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

• Custom LAG3 Antibody Development: Tailor-made solutions to meet specific research requirements.
• Bulk Production: Large-scale antibody manufacturing for industry partners.
• Technical Support: Expert consultation for protocol optimization and troubleshooting.
• Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our LAG3 antibodies, custom preparations, or technical support, contact us at email.