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Otilimab
Otilimab (development codes MOR103 and GSK3196165) is a fully human antibody which has been developed by the biotechnology company MorphoSys. It can also be referred to as HuCAL antibody, HuCAL standing for Human Combinatorial Antibody Library and being a technology used to generate monoclonal antibodies. Otilimab is directed against the granulocyte-macrophage colony stimulating factor (GM-CSF), a monomeric glycoprotein functioning as a cytokine promoting both proliferation and activation of macrophages and neutrophils. Mode of action Otilimab, as its monoclonal antibody, specifically binds to GM-CSF which is consequently neutralised and incapable of binding its targeted inflammatory cells as it should in order to allow their proliferation and activation. There is no following induction of inflammation (through cytokines e.g. TNF-α, IL-1, IL-6), chemotaxis (via chemokines e.g. IL-8), tissue degradation (caused by e.g. MMPs, H2O2) or T and B cell response (following up-re ...
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MorphoSys
MorphoSys AG is a biopharmaceutical company founded in 1992. The company is headquartered near Munich, Germany and has a wholly owned subsidiaryMorphoSys US Inc. in Boston MA in the US. The company has various antibody, protein and peptide technologies that it uses to discover and develop both proprietary and partnered drug candidates. The company has more than 100 drugs in its wider pipeline that are being investigated for a variety of diseases. While many of these are being developed in partnership with pharma and biotech companies, MorphoSys also has a proprietary pipeline with a focus on cancer and autoimmune diseases. MorphoSys AG is listed on the Frankfurt Stock Exchange and on the US Nasdaq stock exchange. History The Company was founded in 1992. In 1999, MorphoSys listed on the Frankfurt Stock Exchange under the ticker symbol "MOR". In 2004, MorphoSys and Novartis entered into a strategic partnership for the research and development of biopharmaceuticals, which was exp ...
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Granulocyte-macrophage Colony-stimulating Factor
Granulocyte-macrophage colony-stimulating factor (GM-CSF), also known as colony-stimulating factor 2 (CSF2), is a monomeric glycoprotein secreted by macrophages, T cells, mast cells, natural killer cells, endothelial cells and fibroblasts that functions as a cytokine. The pharmaceutical analogs of naturally occurring GM-CSF are called sargramostim and molgramostim. Unlike granulocyte colony-stimulating factor, which specifically promotes neutrophil proliferation and maturation, GM-CSF affects more cell types, especially macrophages and eosinophils. Function GM-CSF is a monomeric glycoprotein that functions as a cytokine—it is a white blood cell growth factor. GM-CSF stimulates stem cells to produce granulocytes (neutrophils, eosinophils, and basophils) and monocytes. Monocytes exit the circulation and migrate into tissue, whereupon they mature into macrophages and dendritic cells. Thus, it is part of the immune/ inflammatory cascade, by which activation of a small number ...
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Antibody
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the pathogen, called an antigen. Each tip of the "Y" of an antibody contains a paratope (analogous to a lock) that is specific for one particular epitope (analogous to a key) on an antigen, allowing these two structures to bind together with precision. Using this binding mechanism, an antibody can ''tag'' a microbe or an infected cell for attack by other parts of the immune system, or can neutralize it directly (for example, by blocking a part of a virus that is essential for its invasion). To allow the immune system to recognize millions of different antigens, the antigen-binding sites at both tips of the antibody come in an equally wide variety. In contrast, the remainder of the antibody is relatively constant. It only occurs in a few varia ...
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Cytokine
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrine, paracrine and endocrine signaling as immunomodulating agents. Cytokines include chemokines, interferons, interleukins, lymphokines, and tumour necrosis factors, but generally not hormones or growth factors (despite some overlap in the terminology). Cytokines are produced by a broad range of cells, including immune cells like macrophages, B lymphocytes, T lymphocytes and mast cells, as well as endothelial cells, fibroblasts, and various stromal cells; a given cytokine may be produced by more than one type of cell. They act through cell surface receptors and are especially important in the immune system; cytokines modulate the balance between humoral and cell-based immune responses, and they regulate the maturation, growth, and res ...
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T Helper Cell
The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considered essential in B cell antibody class switching, breaking cross-tolerance in dendritic cells, in the activation and growth of cytotoxic T cells, and in maximizing bactericidal activity of phagocytes such as macrophages and neutrophils. CD4+ cells are mature Th cells that express the surface protein CD4. Genetic variation in regulatory elements expressed by CD4+ cells determines susceptibility to a broad class of autoimmune diseases. Structure and function Th cells contain and release cytokines to aid other immune cells. Cytokines are small protein mediators that alter the behavior of target cells that express receptors for those cytokines. These cells help polarize the immune response depending on the nature of the immunological insult ...
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Food And Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food safety, tobacco products, caffeine products, dietary supplements, Prescription drug, prescription and Over-the-counter drug, over-the-counter pharmaceutical drugs (medications), vaccines, biopharmaceuticals, blood transfusions, medical devices, electromagnetic radiation emitting devices (ERED), cosmetics, Animal feed, animal foods & feed and Veterinary medicine, veterinary products. The FDA's primary focus is enforcement of the Federal Food, Drug, and Cosmetic Act (FD&C), but the agency also enforces other laws, notably Section 361 of the Public Health Service Act, as well as associated regulations. Much of this regulatory-enforcement work is not d ...
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Tuberculosis
Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in which case it is known as latent tuberculosis. Around 10% of latent infections progress to active disease which, if left untreated, kill about half of those affected. Typical symptoms of active TB are chronic cough with blood-containing mucus, fever, night sweats, and weight loss. It was historically referred to as consumption due to the weight loss associated with the disease. Infection of other organs can cause a wide range of symptoms. Tuberculosis is spread from one person to the next through the air when people who have active TB in their lungs cough, spit, speak, or sneeze. People with Latent TB do not spread the disease. Active infection occurs more often in people with HIV/AIDS and in those who smoke. Diagnosis of active TB is ...
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Hepatitis B
Hepatitis B is an infectious disease caused by the ''Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection. Many people have no symptoms during an initial infection. For others, symptoms may appear 30 to 180 days after becoming infected and can include a rapid onset of sickness with nausea, vomiting, yellowish skin, fatigue, dark urine, and abdominal pain. Symptoms during acute infection typically last for a few weeks, though some people may feel sick for up to six months. Deaths resulting from acute stage HBV infections are rare. An HBV infection lasting longer than six months is usually considered chronic. The likelihood of developing chronic hepatitis B is higher for those who are infected with HBV at a younger age. About 90% of those infected during or shortly after birth develop chronic hepatitis B, while less than 10% of those infected after the age of five develop chronic cases. Most of those wit ...
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Tumor Necrosis Factor Alpha
Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homologous TNF domain. As an adipokine, TNF promotes insulin resistance, and is associated with obesity-induced type 2 diabetes. As a cytokine, TNF is used by the immune system for cell signaling. If macrophages (certain white blood cells) detect an infection, they release TNF to alert other immune system cells as part of an inflammatory response. TNF signaling occurs through two receptors: TNFR1 and TNFR2. TNFR1 is constituitively expressed on most cell types, whereas TNFR2 is restricted primarily to endothelial, epithelial, and subsets of immune cells. TNFR1 signaling tends to be pro-inflammatory and apoptotic, whereas TNFR2 signaling is anti-inflammatory and promotes cell proliferation. Suppression of TNFR1 signaling has been important for ...
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Adalimumab
Adalimumab, sold under the brand name Humira, among others, is a monoclonal antibody used to treat rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, plaque psoriasis, hidradenitis suppurativa, uveitis, and juvenile idiopathic arthritis. It is administered by injection under the skin. Common side effects include upper respiratory tract infections, pain at the site of injection, rash, and headache. Other side effects may include serious infections, cancer, anaphylaxis, reactivation of hepatitis B, multiple sclerosis, heart failure, liver failure, and aplastic anemia. Use during pregnancy is not recommended, but some sources show use during breastfeeding may be safe. Adalimumab is a disease-modifying antirheumatic drug (DMARD) and monoclonal antibody that works by inactivating tumor necrosis factor-alpha (TNFα). Adalimumab was approved for medical use in the United States in 2002. It is on the World Health Organization's ...
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Infliximab
Infliximab, a chimeric monoclonal antibody, sold under the brand name Remicade among others, is a medication used to treat a number of autoimmune diseases. This includes Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, and Behçet's disease. It is given by slow injection into a vein, typically at six- to eight-week intervals. Common side effects include infections, acute infusion reactions, and abdominal pain. Infliximab is a chimeric monoclonal antibody biologic. It seems to work by binding to and neutralizing TNF-α, preventing it from interacting with its receptors on the cell. TNF-α is a chemical messenger (cytokine) and a key part of the autoimmune reaction. Infliximab was originally developed in mice as a mouse antibody. Because humans have immune reactions to mouse proteins, the mouse common domains were replaced with similar human antibody domains. They are monoclonal antibodies and have identical ...
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Monoclonal Antibody Therapy
Monoclonal antibody therapy is a form of immunotherapy that uses monoclonal antibodies (mAbs) to bind monospecifically to certain cells or proteins. The objective is that this treatment will stimulate the patient's immune system to attack those cells. Alternatively, in radioimmunotherapy a radioactive dose localizes a target cell line, delivering lethal chemical doses. Antibodies have been used to bind to molecules involved in T-cell regulation to remove inhibitory pathways that block T-cell responses. This is known as immune checkpoint therapy. It is possible to create a mAb that is specific to almost any extracellular/cell surface target. Research and development is underway to create antibodies for diseases (such as rheumatoid arthritis, multiple sclerosis, Alzheimer's disease, Ebola and different types of cancers). Antibody structure and function Immunoglobulin G (IgG) antibodies are large heterodimeric molecules, approximately 150 kDa and are composed of two kinds of ...
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