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Daratumumab Hyaluronidase
Daratumumab, sold under the brand name Darzalex, is an anti-cancer monoclonal antibody medication. It binds to CD38, which is overexpressed in multiple myeloma cells. Daratumumab was originally developed by Genmab, but it is now being jointly developed by Genmab along with the Johnson & Johnson subsidiary Janssen Biotech, which acquired worldwide commercialization rights to the drug from Genmab. Daratumumab was granted breakthrough therapy drug status in 2013, for multiple myeloma. It was granted orphan drug status for multiple myeloma, diffuse large B cell lymphoma, follicular lymphoma, and mantle cell lymphoma. Medical uses In May 2018, the U.S. Food and Drug Administration (FDA) approved daratumumab for use in combination with bortezomib, melphalan and prednisone to include the treatment of people with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant. In the European Union it is indicated as monotherapy for the treatment of adults with ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Fragment Antigen-binding
The fragment antigen-binding region (Fab region) is a region on an antibody that binds to antigens. It is composed of one constant and one variable domain of each of the heavy and the light chain. The variable domain contains the paratope (the antigen-binding site), comprising a set of complementarity-determining regions, at the amino terminal end of the monomer. Each arm of the Y thus binds an epitope on the antigen. Preparation In an experimental setting, Fc and Fab fragments can be generated in the laboratory. The enzyme papain can be used to cleave an immunoglobulin monomer into two Fab fragments and an Fc fragment. Conversely, the enzyme pepsin cleaves below the hinge region, so the result instead is a F(ab')2 fragment and a pFc' fragment. Recently another enzyme for generation of F(ab')2 has been commercially available. The enzyme IdeS (Immunoglobulin degrading enzyme from ''Streptococcus pyogenes'', trade name FabRICATOR) cleaves IgG in a sequence specific manner at ne ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Innate Immune System
The innate, or nonspecific, immune system is one of the two main immunity strategies (the other being the adaptive immune system) in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and is the dominant immune system response found in plants, fungi, insects, and primitive multicellular organisms (see Beyond vertebrates).. The major functions of the innate immune system are to: * recruit immune cells to infection sites by producing chemical factors, including chemical mediators called cytokines * activate the complement cascade to identify bacteria, activate cells, and promote clearance of antibody complexes or dead cells * identify and remove foreign substances present in organs, tissues, blood and lymph, by specialized white blood cells * activate the adaptive immune system through antigen presentation * act as a physical and chemical barrier to infectious agents; via physical measures such as skin and chemical me ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Adenosine
Adenosine (symbol A) is an organic compound that occurs widely in nature in the form of diverse derivatives. The molecule consists of an adenine attached to a ribose via a β-N9-glycosidic bond. Adenosine is one of the four nucleoside building blocks of RNA (and its derivative deoxyadenosine is a building block of DNA), which are essential for all life. Its derivatives include the energy carriers adenosine mono-, di-, and triphosphate, also known as AMP/ADP/ATP. Cyclic adenosine monophosphate (cAMP) is pervasive in signal transduction. Adenosine is used as an intravenous medication for some cardiac arrhythmias. Adenosyl (abbreviated Ado or 5'-dAdo) is the chemical group formed by removal of the 5′-hydroxy (OH) group. It is found in adenosylcobalamin (an active form of vitamin B12) and as a radical in radical SAM enzymes. Medical uses Supraventricular tachycardia In individuals with supraventricular tachycardia (SVT), adenosine is used to help identify and convert t ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Immunosuppression
Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other conditions. In general, deliberately induced immunosuppression is performed to prevent the body from rejecting an organ transplant. Additionally, it is used for treating graft-versus-host disease after a bone marrow transplant, or for the treatment of auto-immune diseases such as systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, or Crohn's disease. This is typically done using medications, but may involve surgery ( splenectomy), plasmapheresis, or radiation. A person who is undergoing immunosuppression, or whose immune system is weak for some other reasons (such as chemotherapy or HIV), is said to be '' immunocompromised''. Deliberately induced Administration of immunosuppressive ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Fragment Crystallizable Region
The fragment crystallizable region (Fc region) is the tail region of an antibody that interacts with cell surface receptors called Fc receptors and some proteins of the complement system. This property allows antibodies to activate the immune system. In IgG, IgA and IgD antibody isotypes, the Fc region is composed of two identical protein fragments, derived from the second and third constant domains of the antibody's two heavy chains; IgM and IgE Fc regions contain three heavy chain constant domains (CH domains 2–4) in each polypeptide chain. The Fc regions of IgGs bear a highly conserved N-glycosylation site. Glycosylation of the Fc fragment is essential for Fc receptor-mediated activity. The N-glycans attached to this site are predominantly core- fucosylated diantennary structures of the complex type. In addition, small amounts of these N-glycans also bear bisecting GlcNAc and α-2,6 linked sialic acid residues. The other part of an antibody, called the Fab regio ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Antibody Opsonization
Antibody opsonization is a process by which a pathogen is marked for phagocytosis. Given normal inflammatory circumstances, microbial pathogen-associated molecular patterns (PAMPs) bind with the endocytic pattern recognition receptors (PRRs) of phagocytes, which mediates neutrophil mediation or macrophage phagocytosis. As well as endocytic PRRs, phagocytes furthermore express opsonin receptors such as Fc receptor and complement receptor 1 (CR1). Should the microbe be coated with opsonising antibodies or C3b complement, the co-stimulation of endocytic PRR and opsonin receptor increases the efficacy of the phagocytic process, enhancing the lysosomal elimination of the infective agent. This mechanism of antibody-mediated increase in phagocytic efficacy is named opsonization. Opsonization involves the binding of an opsonin (e.g., antibody) to an epitope on a pathogen. After opsonin binds to the membrane, phagocytes are attracted to the pathogen. The Fab portion of the antibo ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Complement-dependent Cytotoxicity
Complement-dependent cytotoxicity (CDC) is an effector function of IgG and IgM antibodies. When they are bound to surface antigen on target cell (e.g. bacterial or viral infected cell), the classical complement pathway is triggered by bonding protein C1q to these antibodies, resulting in formation of a membrane attack complex (MAC) and target cell lysis. Complement system is efficiently activated by human IgG1, IgG3 and IgM antibodies, weakly by IgG2 antibodies and it is not activated by IgG4 antibodies. It is one mechanism of action by which therapeutic antibodies or antibody fragments can achieve an antitumor effect. Use of CDC assays Therapeutic antibodies Development of antitumor therapeutic antibodies involves ''in vitro'' analysis of their effector functions including ability to trigger CDC to kill target cells. Classical approach is to incubate antibodies with target cells and source of complement ( serum). Then cell death is determined with several approaches: * ''Ra ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Antibody-dependent Cellular Cytotoxicity
Antibody-dependent cellular cytotoxicity (ADCC), also referred to as antibody-dependent cell-mediated cytotoxicity, is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell, whose membrane-surface antigens have been bound by specific antibodies. It is one of the mechanisms through which antibodies, as part of the humoral immune response, can act to limit and contain infection. ADCC is independent of the immune complement system that also lyses targets but does not require any other cell. ADCC requires an effector cell which classically is known to be natural killer (NK) cells that typically interact with immunoglobulin G (IgG) antibodies. However, macrophages, neutrophils and eosinophils can also mediate ADCC, such as eosinophils killing certain parasitic worms known as helminths via IgE antibodies. In general, ADCC has typically been described as the immune response to antibody-coated cells leading ultimately ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Isatuximab
Isatuximab, sold under the brand name Sarclisa, is a monoclonal antibody (mAb) medication for the treatment of multiple myeloma. The most common side effects include neutropenia (low levels of neutrophils, a type of white blood cell), infusion reactions, pneumonia (infection of the lungs), upper respiratory tract infection (such as nose and throat infections), diarrhoea and bronchitis (inflammation of the airways in the lungs). Isatuximab is an anti-CD38 mAb intended to treat relapsed or refractory multiple myeloma. It entered in Phase II trials for multiple myeloma and T-cell leukemia in 2015. Medical uses In the United States it is indicated, in combination with pomalidomide and dexamethasonevideo about this from ASH 2022, for the treatment of adults with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor. It is also indicated in combination with carfilzomib and dexamethasone, for the treatment of adults ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Amino-acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha amino acids appear in the genetic code. Amino acids can be classified according to the locations of the core structural functional groups, as Alpha and beta carbon, alpha- , beta- , gamma- or delta- amino acids; other categories relate to Chemical polarity, polarity, ionization, and side chain group type (aliphatic, Open-chain compound, acyclic, aromatic, containing hydroxyl or sulfur, etc.). In the form of proteins, amino acid ''residues'' form the second-largest component (water being the largest) of human muscles and other tissues. Beyond their role as residues in proteins, amino acids participate in a number of processes such as neurotransmitter transport and biosynthesis. It is thought that they played a key role in enabling life on ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Epitope
An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The epitope is the specific piece of the antigen to which an antibody binds. The part of an antibody that binds to the epitope is called a paratope. Although epitopes are usually non-self proteins, sequences derived from the host that can be recognized (as in the case of autoimmune diseases) are also epitopes. The epitopes of protein antigens are divided into two categories, conformational epitopes and linear epitopes, based on their structure and interaction with the paratope. Conformational and linear epitopes interact with the paratope based on the 3-D conformation adopted by the epitope, which is determined by the surface features of the involved epitope residues and the shape or tertiary structure of other segments of the antigen. A conformational epitope is formed by the 3-D conformation adopted by the in ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Kell Antigen System
The Kell antigen system (also known as the Kell–Cellano system) is a human blood group system, that is, a group of antigens on the human red blood cell surface which are important determinants of blood type and are targets for autoimmune or alloimmune diseases which destroy red blood cells. The Kell antigens are K, k, Kpa, Kpb, Jsa and Jsb. The Kell antigens are peptides found within the Kell protein, a 93-kilodalton transmembrane zinc-dependent endopeptidase which is responsible for cleaving endothelin-3. Protein The ''KEL'' gene encodes a type II transmembrane glycoprotein that is the highly polymorphic Kell blood group antigen. The Kell glycoprotein links via a single disulfide bond to the XK membrane protein that carries the Kx antigen. The encoded protein contains sequence and structural similarity to members of the neprilysin (M13) family of zinc endopeptidases. There are several alleles of the gene which creates Kell protein. Two such alleles, ''K1'' (Kell) and '' ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
