LAG3 [CAL26]


LAG-3 (Lymphocyte Activation Gene 3) is a surface receptor expressed on activated T cells, an exhaustion marker with immunosuppressive activity (1). Major histocompatibility complex class II (MHC-II) is a ligand for LAG-3; additional ligands (e.g., LSECtin and galectin-3) have also been identified (1,2). Regulatory T cells (Tregs) expressing LAG-3 have enhanced suppressive activity, whereas cytotoxic CD8+ T cells expressing LAG-3 have reduced proliferation rates and effector cytokine production in cancer and autoimmune diabetes (3,4). LAG-3+ tumor-infiltrating lymphocytes (TILs) have been reported in melanoma, colon, pancreatic, breast, lung, hematopoietic, and head and neck cancer patients (5- 11), in association with aggressive clinical features. Antibody-based LAG-3 blockade in multiple cancer mouse models restores CD8+ effector T cells and diminishes Treg populations, an effect enhanced when combined with anti-PD-1 (12). Recent studies in a metastatic ovarian cancer mouse model showed that LAG-3 blockade leads to upregulation of other immune checkpoints (PD-1, CTLA4, and TIM-3), and combination therapy targeting LAG-3, PD-1, and CTLA-4 increases functional cytotoxic T cell levels while reducing Tregs and myeloidderived suppressor cells (13,14). Multiple pre-clinical and clinical studies are testing antagonistic LAG-3 agents in combination with anti-PD-1 and/or anti-CTLA4 therapy (12-15). In view of the activating properties of soluble secreted LAG-3, a soluble agonist LAG-3 antibody (IMP321) was tested in advanced solid malignancies as a single agent (15), and demonstrated sufficient tolerability and efficacy to warrant advancement to phase II (16).



FORMAT ConcentratePredilute
VOLUME 0.1 ml0.5 ml6.0 ml
SOURCE Rabbit Monoclonal
ANTIGEN Synthetic peptide derived from a region of the LAG3 protein
LOCALIZATION Membrane/cytoplasm/Golgi

1. Anderson AC, et al. Lag-3, tim-3, and TIGIT: Co-inhibitory receptors with specialized functions in immune regulation. Immunity. 2016; 44:989-1004.
2. Kouo T, et al. Galectin-3 Shapes Antitumor Immune Responses by Suppressing CD8+ T Cells via LAG-3 and Inhibiting Expansion of Plasmacytoid Dendritic Cells. Cancer Immunol Res. 2015; 3:412-23.
3. Bettini M, et al. Cutting edge: accelerated autoimmune diabetes in the absence of LAG-3. J Immunol. 2011; 187:3493-8.
4. Williams JB, et al. The EGR2 targets LAG3 and 4-1BB describe and regulate dysfunctional antigen-specific CD8+ T cells in the tumor microenvironment. J Exp Med. 2017; 214:381-400.
5. Shapiro M, et al. Lymphocyte activation gene 3: a novel therapeutic target in chronic lymphocytic leukemia, Haematologica. 2017; 102:874–82.
6. Tassi E, et al. Early effector, lymphocytes coexpress multiple inhibitory receptors in primary non-small cell lung cancer. Cancer Res. 2017; 77:851–61.
7. Bottai G, et al. An immune stratification reveals a subset of PD-1/LAG-3 doublepositive triple-negative breast cancers, Breast Cancer Res. 2016; 18:121.
8. Deng WW, et al. LAG-3 confers poor prognosis and its blockade reshapes antitumor response in head and neck squamous cell carcinoma. Oncoimmunology. 2016; 5:e1239005.
9. Llosa NJ, et al. The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints. Cancer Discovery. 2015; 5:43–51.
10. Meng Q, et al. Expansion of tumor-reactive T cells from patients with pancreatic cancer. J Immunother. 2016; 39:81–9.
11. Demeure CE, et al. T Lymphocytes infiltrating various tumour types express the MHC class II ligand lymphocyte activation gene-3 (LAG-3): role of LAG-3/MHC class II interactions in cell–cell contacts. Eur J Cancer. 2001; 37:1709–18.
12. Woo SR, et al. Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer Res. 2012; 72(4):917-27.
13. Huang RY, et al. LAG3 and PD1 co-inhibitory molecules collaborate to limit CD8+ T cell signaling and dampen antitumor immunity in a murine ovarian cancer model. Oncotarget. 2015; 6:27359-77.
14. Huang RY, et al. Compensatory upregulation of PD-1, LAG-3, and CTLA-4 limits the efficacy of single-agent checkpoint blockade in metastatic ovarian cancer. Oncoimmunology. 2017; 6:e1249561.
15. Baumeister SH, et al. Coinhibitory pathways in immunotherapy for cancer. Annu Rev Immunol. 2016; 34:539-73.
16. Legat A, et al. Vaccination with LAG-3Ig (IMP321) and Peptides Induces Specific CD4 and CD8 T-Cell Responses in Metastatic Melanoma Patients–Report of a Phase I/IIa Clinical Trial. Clin Cancer Res. 2016 Mar 15;22(6):1330-40.
17. Center for Disease Control Manual. Guide: Safety Management, NO. CDC-22, Atlanta, GA. April 30, 1976 “Decontamination of Laboratory Sink Drains to Remove Azide Salts.”
18. Clinical and Laboratory Standards Institute (CLSI). Protection of Laboratory Workers from Occupationally Acquired Infections; Approved Guideline-Fourth Edition CLSI document M29-A4 Wayne, PA 2014.


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