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LAG-3
Lymphocyte-activation gene 3, also known as LAG-3, is a protein which in humans is encoded by the ''LAG3'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba .... LAG3, which was discovered in 1990 and was designated CD223 ( cluster of differentiation 223) after the Seventh Human Leucocyte Differentiation Antigen Workshop in 2000, is a cell surface molecule with diverse biologic effects on T cell function. It is an immune checkpoint receptor and as such is the target of various drug development programs by pharmaceutical companies seeking to develop new treatments for cancer and autoimmune disorders. In soluble form it is also being developed as a cancer drug in its own right. Gene The LAG3 gene contains 8 exons. The sequence data, exon/intron organization, and chromosomal loca ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
IMP321
Eftilagimod alpha ( INN; development code IMP321 or efti) is a large-molecule cancer drug being developed by the clinical-stage biotechnology company Immutep. Efti is a soluble version of the immune checkpoint molecule LAG-3. It is an APC Activator used to increase an immune response to tumors, and is administered by subcutaneous injection. Efti has three intended clinical settings: * as adjuvant to cancer vaccines (in a low, effective dose of ~250 µg) * as first-line 'chemo-immunotherapy,' that is, combined with standard chemotherapy (e.g. paclitaxel) * in combination immunotherapy with PD-1 treatments (e.g. pembrolizumab) Eftilagimod alpha is in Phase II clinical testing. Currently, the main indications for the drug are metastatic breast cancer, non-small cell lung cancer (NSCLC), and head and neck squamous cell carcinoma (HNSCC). Background Eftilagimod alpha ("efti" in short) is a soluble LAG-3 fusion protein that activates antigen-presenting cells. It is a 1 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Immutep
Immutep Ltd (formerly Prima Biomed) is a biotechnology company working primarily in the field of cancer immunotherapy using the LAG3 immune control mechanism. The company was originally built on CVac, a therapeutic cancer vaccine. In late 2014 the privately held French immunotherapy company Immutep SA was purchased by Prima Biotech. Prima currently has three main products in its pipeline, all acquired with Immutep: Eftilagimod alpha, (lab name: IMP321) which is recombinant soluble LAG-3, used as an activator of antigen presenting cells. This product has completed a Phase IIa clinical study, where it doubled the expected response rate in HER2-negative metastatic breast cancer. IMP731, a depleting monoclonal antibody for autoimmune diseases, targeting LAG-3+ activated T cells. This antibody has been licensed to GlaxoSmithKline. IMP701, an antagonist monoclonal antibody to LAG3 for use in cancer. This product has been licensed to Novartis History Immutep (formerly Prim ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Frédéric Triebel
Frédéric Triebel (born 20 November 1954) is a French immunologist who is best known for his 1990 discovery of the LAG3 immune control mechanism. Triebel worked through the 1990s in a collaboration between Institut Gustave Roussy and Merck Serono to establish LAG-3's mechanism of action in T cells and dendritic cells. In 2001 he founded Immutep SA, a biotech company, to develop the therapeutic potential of LAG3. In 2014 this company was acquired by Prima BioMed, where Triebel remains Chief Scientific and Medical Officer. Early life and education He completed his Doctor of Medicine degree at Poitiers University in 1981 and then a four-year clinical hematology fellowship in Paris hospitals. In 1983, Frédéric Triebel received the Gold Medal of the Paris Medicine University. In parallel, Triebel gained a PhD in Immunology at the University of Paris VI in 1985. His PhD thesis was in the field of immunogenetics, focused on the mechanisms that activate human antigen-specific T ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
GSK2831781
GSK2831781 is a monoclonal antibody being developed by GlaxoSmithKline (GSK) for autoimmune diseases. The antibody targets the T cell activation marker LAG-3, which is mainly expressed in inflamed tissues. In GSK's March 2015 ''Product development pipeline'' document the antibody is listed under 'Immuno-inflammation' candidates. GSK2831781 entered a Phase I clinical trial in psoriasis early in 2015. History GSK2831781 originated from a chimeric monoclonal antibody to LAG-3 developed in 2008 by the French biotechnology company Immutep. That company had been built around drugs targeting LAG-3 and was associated with Frédéric Triebel, an immunologist generally regarded as a leading authority on LAG-3. In discovering the Immutep antibody, Triebel worked with two researchers from the University of Nantes, where there was an INSERM unit focused on transplantation immunology called ITUN (Institut de Transplantation Urologie Nephrologie). Triebel et al. codenamed their initial m ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Relatlimab
Relatlimab is a monoclonal antibody designed for the treatment of melanoma. It is used in combination with nivolumab to treat melanoma. Relatlimab is a Lymphocyte activation gene-3 (LAG-3) inhibitor. It is under development by Bristol-Myers Squibb. It is made using Chinese hamster ovary cells. History , relatlimab is undergoing Phase II/III trials. The combination nivolumab/relatlimab (Opdualag) was approved for medical use in the United States in March 2022. Names Relatlimab is the United States Adopted Name A United States Adopted Name (USAN) is a unique nonproprietary name assigned to a medication marketed in the United States. Each name is assigned by the USAN Council, which is co-sponsored by the American Medical Association (AMA), the United Sta ... (USAN) and the international nonproprietary name (INN). References External links * Bristol Myers Squibb Clinical trials sponsored by Bristol Myers Squibb Experimental drugs Monoclonal antibodies for ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
FGL1
Fibrinogen-like protein 1 (FGL-1) is a protein that is structurally related to fibrinogen. In humans, FGL-1 is encoded by the ''FGL1'' gene. Four splice variants exist for this gene. Function Fibrinogen-like protein 1 is a member of the fibrinogen family of proteins, which also includes fibrinogen, fibrinogen-like protein 2, and clotting factors V, VIII, and XIII. FGL-1 is homologous to the carboxy terminus of the fibrinogen beta- and gamma- subunits which contains the four conserved cysteines of that are common to all members of the fibrinogen family. However, FGL-1 lacks the platelet-binding site, cross-linking region, and thrombin-sensitive site which allow the other members of the fibrinogen family to aid in fibrin clot formation. FGL-1 has also been observed to strongly bind to and activate LAG-3, a regulatory protein expressed on T cells. As LAG-3 has an important role in controlling activated T cells, manipulating FGL-1 binding to T cells has been proposed for bo ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Immune Checkpoint
Immune checkpoints are regulators of the immune system. These pathways are crucial for self-tolerance, which prevents the immune system from attacking cells indiscriminately. However, some cancers can protect themselves from attack by stimulating immune checkpoint targets. Inhibitory checkpoint molecules are targets for cancer immunotherapy due to their potential for use in multiple types of cancers. Currently approved checkpoint inhibitors block CTLA4 and PD-1 and PD-L1. For the related basic science discoveries, James P. Allison and Tasuku Honjo won the Tang Prize in Biopharmaceutical Science and the Nobel Prize in Physiology or Medicine in 2018. Stimulatory checkpoint molecules Four stimulatory checkpoint molecules are members of the tumor necrosis factor (TNF) receptor superfamily—CD27, CD40, OX40, GITR and CD137. Another two stimulatory checkpoint molecules belong to the B7-CD28 superfamily—CD28 itself and ICOS. * CD27: This molecule supports antigen-speci ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Treg
The regulatory T cells (Tregs or Treg cells), formerly known as suppressor T cells, are a subpopulation of T cells that modulate the immune system, maintain tolerance to self-antigens, and prevent autoimmune disease. Treg cells are immunosuppressive and generally suppress or downregulate induction and proliferation of effector T cells. Treg cells express the biomarkers CD4, FOXP3, and CD25 and are thought to be derived from the same lineage as naïve CD4+ cells. Because effector T cells also express CD4 and CD25, Treg cells are very difficult to effectively discern from effector CD4+, making them difficult to study. Research has found that the cytokine transforming growth factor beta (TGF-β) is essential for Treg cells to differentiate from naïve CD4+ cells and is important in maintaining Treg cell homeostasis. Mouse models have suggested that modulation of Treg cells can treat autoimmune disease and cancer and can facilitate organ ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
T Cell Activation
A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell surface. T cells are born from hematopoietic stem cells, found in the bone marrow. Developing T cells then migrate to the thymus gland to develop (or mature). T cells derive their name from the thymus. After migration to the thymus, the precursor cells mature into several distinct types of T cells. T cell differentiation also continues after they have left the thymus. Groups of specific, differentiated T cell subtypes have a variety of important functions in controlling and shaping the immune response. One of these functions is immune-mediated cell death, and it is carried out by two major subtypes: CD8+ "killer" and CD4+ "helper" T cells. (These are named for the presence of the cell surface proteins ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Regulatory T Cell
The regulatory T cells (Tregs or Treg cells), formerly known as suppressor T cells, are a subpopulation of T cells that modulate the immune system, maintain tolerance to self-antigens, and prevent autoimmune disease. Treg cells are immunosuppressive and generally suppress or downregulate induction and proliferation of effector T cells. Treg cells express the biomarkers CD4, FOXP3, and CD25 and are thought to be derived from the same lineage as naïve CD4+ cells. Because effector T cells also express CD4 and CD25, Treg cells are very difficult to effectively discern from effector CD4+, making them difficult to study. Research has found that the cytokine transforming growth factor beta (TGF-β) is essential for Treg cells to differentiate from naïve CD4+ cells and is important in maintaining Treg cell homeostasis. Mouse models have suggested that modulation of Treg cells can treat autoimmune disease and cancer and can facilitat ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
T Cell
A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell surface. T cells are born from hematopoietic stem cells, found in the bone marrow. Developing T cells then migrate to the thymus gland to develop (or mature). T cells derive their name from the thymus. After migration to the thymus, the precursor cells mature into several distinct types of T cells. T cell differentiation also continues after they have left the thymus. Groups of specific, differentiated T cell subtypes have a variety of important functions in controlling and shaping the immune response. One of these functions is immune-mediated cell death, and it is carried out by two major subtypes: CD8+ "killer" and CD4+ "helper" T cells. (These are named for the presence of the cell surface proteins ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Checkpoint Inhibitor
Checkpoint inhibitor therapy is a form of cancer immunotherapy. The therapy targets immune checkpoints, key regulators of the immune system that when stimulated can dampen the immune response to an immunologic stimulus. Some cancers can protect themselves from attack by stimulating immune checkpoint targets. Checkpoint therapy can block inhibitory checkpoints, restoring immune system function. The first anti-cancer drug targeting an immune checkpoint was ipilimumab, a CTLA4 blocker approved in the United States in 2011. Currently approved checkpoint inhibitors target the molecules CTLA4, PD-1, and PD-L1. PD-1 is the transmembrane programmed cell death 1 protein (also called PDCD1 and CD279), which interacts with PD-L1 ( PD-1 ligand 1, or CD274). PD-L1 on the cell surface binds to PD-1 on an immune cell surface, which inhibits immune cell activity. Among PD-L1 functions is a key regulatory role on T cell activities. It appears that (cancer-mediated) upregulation of PD-L1 on th ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
