LAG-3 Antibody (17B4) - BSA Free

Lymphocyte activation gene-3 (LAG-3), also referred to as CD233, is a type I transmembrane protein with a theoretical molecular weight of 70 kDa that is a member of the immunoglobulin superfamily (IgSF) (1, 2). Human LAG-3 cDNA encodes 525 amino acids (aa) that includes a 28 aa signal sequence, a 422 aa extracellular domain (ECD) with four Ig-like domains (D1-D4), a transmembrane region and a highly charged cytoplasmic region. Within the ECD, human LAG-3 shares 70%, 67%, 76%, and 73% aa sequence identity with mouse, rat, porcine, and bovine LAG-3, respectively. The extracellular region of LAG-3 and the CD4 co-receptor share ~20% aa sequence homology but are structurally similar and both bind to major histocompatibility complex class II (MHCII) on antigen-presenting cells (APCs), although LAG-3 has much higher affinity (1, 3). LAG-3 is highly expressed in the lymph node, spleen, ovary, and appendix while expressed at a lower level in a variety of other tissues. More specifically, LAG-3 is expressed on activated CD4+ and CD8+ T cells, natural killer T (NKT) cells, natural killer (NK) cells, plasmacytoid dendritic cells (pDCs), and regulatory T cells (Tregs), but not on naive, or resting, T cells (1, 3).

As mentioned above, LAG-3 binds to MHCII and this occurs via a proline-rich amino acid loop in D1 (1, 3). Another unique feature of LAG-3 is the longer connecting peptide region between the D4 and the transmembrane, which is acted upon and cleaved by metalloproteinases a disintegrin and metallopeptidase domain (ADAM) 10 and ADAM17 to generate a soluble 54 kDa form of LAG-3 (sLAG-3) (1, 3). The interaction of LAG-3 with MHCII prevents the MHC molecule from binding to a T-cell receptor (TCR) or CD4, thereby functioning in an inhibitory role and suppressing the TCR signal (4). When LAG-3 crosslinks with the TCR/CD3 complex, it causes reduced T-cell proliferation and cytokine secretion (4). This negative regulation is important in controlling autoimmunity as one study found Lag3-/- NOD (non-obese diabetic) mice had accelerated diabetes onset and increased T-cell infiltration into islet cells (5). On the other hand, besides being a negative regulator of T-cells, LAG-3 binding to MHCII molecules on APCs induces dendritic cell maturation and cytokine secretion by monocytes (5, 6). In addition to MHCII, other reported ligands for LAG-3 includes fibrinogen-like protein 1 (FGL1), liver endothelial cell lectin (lSECtin), galectin-3 (Gal-3), and alpha-synuclein fibrils (1). Gal-3, for instance, is expressed on stromal cells and CD8+ T-cells in the tumor microenvironment and the interaction with LAG-3 was shown to be crucial for the suppression of secreted cytokine IFN-gamma and may control anti-tumor immune responses (1, 5). Interestingly, a mouse model of Parkinson's disease revealed LAG-3 binding to alpha-synuclein fibrils in the central nervous system, contributing to its pathogenesis (1, 5).

Recent cancer immunotherapeutic approaches have focused on inhibitory receptors such as LAG-3 to revive expression of cytotoxic T-cells to attack tumors (6). LAG-3 has been shown to be co-expressed and have synergy with another immune-checkpoint molecule called programmed-death 1 (PD-1) (1, 4, 5, 6). In a mouse model of colon adenocarcinoma LAG3 blockade alone was largely ineffective, however co-blockade of LAG-3 and PD-1 limited tumor growth and resulted in tumor clearance in 80% of mice, compared to 40% with PD-1 blockade alone (5). Additionally, in a model of fibrosarcoma the LAG-3/PD-1 duel blockade increased survival and the percentage of tumor-free mice (5). Analysis of a variety of human tumor samples (e.g. melanoma, colon cancer, head and neck squamous cell carcinoma) also suggest that LAG3 alone and combinatorial treatment with PD-1 may be a good target for treatment (1, 3-6). To date there are over 10 different agents targeting LAG-3 in clinical trials for cancer either as an anti-LAG-3 blocking antibody monotherapy or as a combination antagonist bispecific antibody, primarily with PD-1 (1, 3-6).

Alternative names for LAG-3 includes 17b4 lag3, 17b4 neutralizing, 17b4, CD223, FDC, LAG-3 17b4, LAG-3 blocking, and LAG3.

References

1. Maruhashi, T., Sugiura, D., Okazaki, I. M., & Okazaki, T. (2020). LAG-3: from molecular functions to clinical applications. Journal for Immunotherapy of Cancer, 8(2), e001014. https://doi.org/10.1136/jitc-2020-001014

2. Triebel, F., Jitsukawa, S., Baixeras, E., Roman-Roman, S., Genevee, C., Viegas-Pequignot, E., & Hercend, T. (1990). LAG-3, a novel lymphocyte activation gene closely related to CD4. The Journal of experimental medicine, 171(5), 1393-1405. https://doi.org/10.1084/jem.171.5.1393

3. Ruffo, E., Wu, R. C., Bruno, T. C., Workman, C. J., & Vignali, D. (2019). Lymphocyte-activation gene 3 (LAG3): The next immune checkpoint receptor. Seminars in immunology, 42, 101305. https://doi.org/10.1016/j.smim.2019.101305

4. Long, L., Zhang, X., Chen, F., Pan, Q., Phiphatwatchara, P., Zeng, Y., & Chen, H. (2018). The promising immune checkpoint LAG-3: from tumor microenvironment to cancer immunotherapy. Genes & cancer, 9(5-6), 176-189.

5. Andrews, L. P., Marciscano, A. E., Drake, C. G., & Vignali, D. A. (2017). LAG3 (CD223) as a cancer immunotherapy target. Immunological reviews, 276(1), 80-96. https://doi.org/10.1111/imr.12519

6. Goldberg, M. V., & Drake, C. G. (2011). LAG-3 in Cancer Immunotherapy. Current topics in microbiology and immunology, 344, 269-278. https://doi.org/10.1007/82_2010_114

This product is for research use only and is not approved for use in humans or in clinical diagnosis. Primary Antibodies are guaranteed for 1 year from date of receipt.

We have publications tested in 2 confirmed species: Human, Primate.

We have publications tested in 3 applications: FLOW, Flow, IF/IHC.

Showing Publications 1 - 10 of 18. Show All 18 Publications. Collapse Publications.

Publications using NBP1-97657	Applications	Species
Li K, Tandurella JA, Gai J et al. Multi-omic analyses of changes in the tumor microenvironment of pancreatic adenocarcinoma following neoadjuvant treatment with anti-PD-1 therapy Cancer cell 2022-10-21 [PMID: 36306792] (IF/IHC, Human)	IF/IHC	Human
Rappold PM, Vuong L, Leibold J et al. A Targetable Myeloid Inflammatory State Governs Disease Recurrence in Clear Cell Renal Cell Carcinoma Cancer discovery 2022-06-27 [PMID: 35758895]
El Halabi L, Adam J, Gravelle P et al. Expression of the Immune Checkpoint Regulators LAG-3 and TIM-3 in Classical Hodgkin Lymphoma Clinical Lymphoma Myeloma and Leukemia 2020-11-01 [PMID: 33277223] (IF/IHC, Human) Details: Immunohistochemical analysis of biopsies from patients with classic Hodgkins lymphoma.	IF/IHC	Human
Dummer R, Lebbe C, Atkinson V et al. Combined PD-1, BRAF and MEK inhibition in advanced BRAF-mutant melanoma: safety run-in and biomarker cohorts of COMBI-i Nat Med 2020-10-01 [PMID: 33020648]
Harper J, Gordon S, Chan C et Al. CTLA-4 and PD-1 dual blockade induces SIV reactivation without control of rebound after antiretroviral therapy interruption Nat Med. [PMID: 32284611] (FLOW, Primate)	FLOW	Primate
Pericart S, Tosolini M, Gravelle P et al. Profiling Immune Escape in Hodgkin's and Diffuse large B-Cell Lymphomas Using the Transcriptome and Immunostaining Cancers (Basel) 2018-10-31 [PMID: 30384489] (IF/IHC, Human) Details: Citation using the FITC form of this antibody.	IF/IHC	Human
Wang J, Ti Y, Wang Y et al. LAG-3 Represents a Marker of CD4+ T Cells with Regulatory Activity in Patients with Bone Fracture. Immunol. Invest. 2018-04-19 [PMID: 29671649] (Human)		Human
Sabins NC, Chornoguz O, Leander K et al. TIM-3 Engagement Promotes Effector Memory T Cell Differentiation of Human Antigen-Specific CD8 T Cells by Activating mTORC1 J. Immunol. 2017 Nov 10 [PMID: 29127145] (Flow, Human)	Flow	Human
Ma QY, Huang DY, Zhang HJ et al. Function and regulation of LAG3 on CD4(+)CD25(-) T cells in non-small cell lung cancer Exp. Cell Res. 2017-09-19 [PMID: 28935468] (Human)		Human
Casati C, Camisaschi C, Novellino L et al. Human lymphocyte activation gene-3 molecules expressed by activated T cells deliver costimulation signal for dendritic cell activation. J Immunol. 2008 Mar. [PMID: 18322184]
Triebel F, Hacene K, Pichon MF et al. A soluble lymphocyte activation gene-3 (sLAG-3) protein as a prognostic factor in human breast cancer expressing estrogen or progesterone receptors. Cancer Lett. 2006 Apr. [PMID: 15946792]
Macon-Lemaitre L, Triebel F. The negative regulatory function of the lymphocyte-activation gene-3 co-receptor (CD223) on human T cells. Immunology 2005-05-31 [PMID: 15885122] Details: Citation using the FITC format of this antibody.
Di Carlo E, Cappello P, Sorrentino C et al. Immunological mechanisms elicited at the tumour site by lymphocyte activation gene-3 (LAG-3) versus IL-12: sharing a common Th1 anti-tumour immune pathway. J Pathol. 2005-01-01 [PMID: 15586367]
Demeure CE, Wolfers J, Martin-Garcia N 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 Sep. [PMID: 11527700]
Hannier S, Tournier M, Bismuth G et al. CD3/TCR complex-associated lymphocyte activation gene-3 molecules inhibit CD3/TCR signaling. J Immunol. 1998 Oct. [PMID: 9780176]
Huard B, Mastrangeli R, Prigent P et al. Characterization of the major histocompatibility complex class II binding site on LAG-3 protein. Proc Natl Acad Sci U S A. 1997 May [PMID: 9159144]
Huard B, Gaulard P, Faure F et al. Cellular expression and tissue distribution of the human LAG-3-encoded protein, an MHC class II ligand. Immunogenetics. 1994-01-01 [PMID: 7506235]
Baixeras E, Huard B, Miossec C et al. Characterization of the lymphocyte activation gene 3-encoded protein. A new ligand for human leukocyte antigen class II antigens. J Exp Med. 1992-08-01 [PMID: 1380059]
Show All 18 Publications. Collapse Publications.

Images	Ratings	Applications	Species	Date	Details
Enlarge	4 reviewed by: Verified Customer	Immunofluorescence - frozen	Human	03/07/2020	View Summary Application Other Sample Tested human tonsil Species Human Lot N/A
Enlarge	5 reviewed by: Verified Customer	IHC-P	Human	01/23/2018	View Summary Application Immunohistochemistry-Paraffin Sample Tested Tonsil Species Human Lot 02011620

Array NBP1-97657

• LAG-3 Antibodies
• LAG-3 Antibody Pack
• LAG-3 ELISA Kit
• LAG-3 Lysate
• LAG-3 Protein
• LAG-3 ELISA
• LAG-3 Proteins and Enzymes