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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 ...
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Prima BioMed
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 Novartis AG is a Swiss multi ...
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IMP731
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 ...
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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 biological effects on T cell function but overall has an immune inhibitory effect. 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. LAG-3 is closely related to CD4, with which it shares the ability to bind MHC class II molecules. Although there has been conflicting information on which motifs in the LAG-3 cytoplasmic tail are important for function, evolutionary conversation patterns combined with functional studies imply that the evolutiona ...
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Monoclonal Antibody
A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies are identical and can thus have monovalent affinity, binding only to a particular epitope (the part of an antigen that is recognized by the antibody). In contrast, polyclonal antibodies are mixtures of antibodies derived from multiple plasma cell lineages which each bind to their particular target epitope. Artificial antibodies known as bispecific monoclonal antibodies can also be engineered which include two different antigen binding sites ( FABs) on the same antibody. It is possible to produce monoclonal antibodies that specifically bind to almost any suitable substance; they can then serve to detect or purify it. This capability has become an investigative tool in biochemistry, molecular biology, and medicine. Monoclonal antibod ...
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Corticosteroids
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involved in a wide range of physiological processes, including stress response, immune response, and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte levels, and behavior. Some common naturally occurring steroid hormones are cortisol (), corticosterone (), cortisone () and aldosterone () (cortisone and aldosterone are isomers). The main corticosteroids produced by the adrenal cortex are cortisol and aldosterone. The etymology of the '' cortico-'' part of the name refers to the adrenal cortex, which makes these steroid hormones. Thus a corticosteroid is a "cortex steroid". Classes * Glucocorticoids such as cortisol affect carbohydrate, fat, and protein metabolism, and have anti-inflam ...
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Cytotoxicity
Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are toxic metals, toxic chemicals, microbe neurotoxins, radiation particles and even specific neurotransmitters when the system is out of balance. Also some types of drugs, e.g alcohol, and some venom, e.g. from the puff adder (''Bitis arietans'') or brown recluse spider (''Loxosceles reclusa'') are toxic to cells. Cell physiology Treating cells with the cytotoxic compound can result in a variety of prognoses. The cells may undergo necrosis, in which they lose membrane integrity and die rapidly as a result of cell lysis. The cells can stop actively growing and dividing (a decrease in cell viability), or the cells can activate a genetic program of controlled cell death (apoptosis). Cells undergoing necrosis typically exhibit rapid swelling, lose membrane integrity, shut down metabolism, and release their contents into the environment. Cells that undergo rapid necrosis in vitro do not have sufficient ...
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Humanized Antibody
Humanized antibodies are antibodies from non-human species whose protein sequences have been modified to increase their similarity to antibody variants produced naturally in humans. The process of "humanization" is usually applied to monoclonal antibodies developed for administration to humans (for example, antibodies developed as anti-cancer drugs). Humanization can be necessary when the process of developing a specific antibody involves generation in a non-human immune system (such as that in mice). The protein sequences of antibodies produced in this way are partially distinct from homologous antibodies occurring naturally in humans, and are therefore potentially immunogenic when administered to human patients (see also Human anti-mouse antibody). Until 2021, the International Nonproprietary Names of new humanized antibodies ended in ''-zumab'', as in ''omalizumab'', but a new nomenclature has since been adopted and new names now end in different stems (see Nomenclature of mon ...
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Afucosylated Monoclonal Antibodies
Afucosylated monoclonal antibodies are monoclonal antibodies engineered so that the oligosaccharides in the Fc region of the antibody do not have any fucose sugar units. When antibodies are afucosylated, antibody-dependent cellular cytotoxicity (ADCC) is increased. Background Most approved monoclonal antibodies are of the IgG1 isotype, where two N-linked biantennary complex-type oligosaccharides are bound to the Fc region. The Fc region exercises the effector function of ADCC through its interaction with leukocyte receptors of the FcγR family. ADCC is important in the efficacy of cancer antibodies, but with many approved cancer antibodies there is less ADCC than could be desired due to nonspecific IgG competing with the drugs for binding to FcγIIIa on natural killer cells. Afucosylated monoclonal antibodies overcome this problem through improved FcγIIIa binding. Approaches The Swiss company GlycArt Biotechnology developed a system using CHO cells, where the cells were engin ...
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Transplantation (journal)
''Transplantation'' is a peer-reviewed medical journal covering transplantation medicine. The editor-in-chief is Stefan G. Tullius (Harvard University). It was established in 1963 and is published by Wolters Kluwer on behalf of The Transplantation Society. Its sister journal, '' Transplantation Direct'', is an online-only open access, peer-reviewed medical journal also covering transplantation medicine, established in 2015. The journal's editor-in-chief is Edward K. Geissler (University of Regensburg). Abstracting and indexing The journal is abstracted and indexed in: According to the ''Journal Citation Reports'', the journal has a 2023 impact factor The impact factor (IF) or journal impact factor (JIF) of an academic journal is a type of journal ranking. Journals with higher impact factor values are considered more prestigious or important within their field. The Impact Factor of a journa ... of 5.5, ranking it 38 out of 181 journals in the category "Immunology", 14 out ...
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Medical Literature
Medical literature is the scientific literature of medicine: articles in journals and texts in books devoted to the field of medicine. Many references to the medical literature include the health care literature generally, including that of dentistry, veterinary medicine, pharmacy, nursing, and the allied health professions. Contemporary and historic views regarding diagnosis, prognosis and treatment of medical conditions have been documented for thousands of years. The Edwin Smith papyrus is the first known medical treatise. Ancient medical literature often described inflictions related to warfare. History Throughout history, people have written about diseases, how human beings might contract them and what could be done to remedy it. Medicine ranged from folklore and witchcraft to modern evidence-based medicine. Among the most notable early medical descriptions are found in texts from Egypt (''Edwin Smith Papyrus'', ''Ebers Papyrus'', '' Kahun Gynecological Papyrus''), Meso ...
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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 kills 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 to the l ...
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