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LAG3
Lymphocyte-activation gene 3, also known as LAG-3, is a protein which in humans is encoded by the ''LAG3'' gene. 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 localization all indicate a close relationship of LAG3 to CD4. The gene for LAG-3 lies adjacent to the gene for CD4 on human chromosome 12 (12p13) and is approximately 20% identical to the CD4 gene. Protein The LAG3 protein, which belongs to immunoglobulin ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific 3D structure that determines its activity. A linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide. Short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called peptides. The individual amino acid residues are bonded together by peptide bonds and adjacent amino acid residues. The sequence of amino acid ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CTLA-4
CTLA-4 or CTLA4 (cytotoxic T-lymphocyte-associated protein 4), also known as CD152 ( cluster of differentiation 152), is a protein receptor that functions as an immune checkpoint and downregulates immune responses. CTLA-4 is constitutively expressed in regulatory T cells but only upregulated in conventional T cells after activation – a phenomenon which is particularly notable in cancers. It acts as an "off" switch when bound to CD80 or CD86 on the surface of antigen-presenting cells. The CTLA-4 protein is encoded by the ''Ctla-4'' gene in mice and the ''CTLA-4'' gene in humans. History CTLA-4 was first identified in 1991 as a second receptor for the T cell costimulation ligand B7. In November 1995, the labs of Tak Wah Mak and Arlene H. Sharpe independently published their findings on the discovery of the function of CTLA-4 as a negative regulator of T-cell activation, by knocking out the gene in mice. Previous studies from several labs had used methods which could n ... [...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 Prima ... [...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-c ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Plaque Psoriasis
Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by raised areas of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small, localized patches to complete body coverage. Injury to the skin can trigger psoriatic skin changes at that spot, which is known as the Koebner phenomenon. The five main types of psoriasis are plaque, guttate, inverse, pustular, and erythrodermic. Plaque psoriasis, also known as psoriasis vulgaris, makes up about 90% of cases. It typically presents as red patches with white scales on top. Areas of the body most commonly affected are the back of the forearms, shins, navel area, and scalp. Guttate psoriasis has drop-shaped lesions. Pustular psoriasis presents as small, noninfectious, pus-filled blisters. Inverse psoriasis forms red patches in skin folds. Erythrodermic psoriasis occurs when the rash becomes very widespread, and can develop from any of the other types. ... [...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 initia ... [...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 facilitate org ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PD-1
Programmed cell death protein 1, also known as PD-1 and CD279 (cluster of differentiation 279), is a protein on the surface of T and B cells that has a role in regulating the immune system's response to the cells of the human body by down-regulating the immune system and promoting self-tolerance by suppressing T cell inflammatory activity. This prevents autoimmune diseases, but it can also prevent the immune system from killing cancer cells. PD-1 is an immune checkpoint and guards against autoimmunity through two mechanisms. First, it promotes apoptosis (programmed cell death) of antigen-specific T-cells in lymph nodes. Second, it reduces apoptosis in regulatory T cells (anti-inflammatory, suppressive T cells). PD-1 inhibitors, a new class of drugs that block PD-1, activate the immune system to attack tumors and are used to treat certain types of cancer. The PD-1 protein in humans is encoded by the ''PDCD1'' gene. PD-1 is a cell surface receptor that belongs to the immunoglob ... [...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 the c ... [...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] |
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 160 k ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Dendritic Cell
Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. They act as messengers between the innate and the adaptive immune systems. Dendritic cells are present in those tissues that are in contact with the external environment, such as the skin (where there is a specialized dendritic cell type called the Langerhans cell) and the inner lining of the nose, lungs, stomach and intestines. They can also be found in an immature state in the blood. Once activated, they migrate to the lymph nodes where they interact with T cells and B cells to initiate and shape the adaptive immune response. At certain development stages they grow branched projections, the '' dendrites'' that give the cell its name (δένδρον or déndron being Greek for 'tree'). While similar in appearance, these are structure ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
