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SGN-CD19A
Denintuzumab mafodotin (INN; development codes SGN-19A or SGN-CD19A) is a humanized monoclonal antibody-drug conjugate designed for the treatment of CD19-positive acute lymphoblastic leukemia and B-cell non-Hodgkin lymphoma. It consists of an anti-CD19 mAb linked to monomethyl auristatin F (MMAF), a cytotoxic agent. This drug was developed by Seattle Genetics. ''Denintuzumab'' refers to the anti-CD19 antibody, and ''mafodotin'' refers to MMAF and the chemical linkage. Clinical trials The drug is in phase I clinical trials. Preliminary phase I results for B-cell malignancies, including diffuse large B-cell lymphoma Diffuse large B-cell lymphoma (DLBCL) is a cancer of B cells, a type of lymphocyte that is responsible for producing antibody, antibodies. It is the most common form of non-Hodgkin lymphoma among adults, with an annual Incidence (epidemiology), in ... (DLBCL) and B-lineage acute lymphocytic leukemia (B-ALL) were presented at the ASH medical conference Dec 2015. Pha ...
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Monomethyl Auristatin F
Monomethyl auristatin F (MMAF) is a synthetic antineoplastic agent. It is part of the approved drug belantamab mafodotin in multiple myeloma and some experimental anti-cancer antibody-drug conjugates such as vorsetuzumab mafodotin and SGN-CD19A. In International Nonproprietary Names for MMAF-antibody-conjugates, the name mafodotin refers to MMAF plus its attachment structure to the antibody. Mechanism of action Monomethyl auristatin F is an antimitotic agent which inhibits cell division by blocking the polymerisation of tubulin. It is linked to an antibody with high affinity to structures on cancer cells, causing MMAF to accumulate in such cells. Chemistry MMAF is actually desmethyl-auristatin F; that is, the N-terminal amino group has only one methyl substituent instead of two as in auristatin F itself. See also * Monomethyl auristatin E Monomethyl auristatin E (MMAE) is a synthetic antineoplastic agent. Because of its toxicity, it cannot be used as a drug itself; instea ...
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CD19
B-lymphocyte antigen CD19, also known as CD19 molecule ( Cluster of Differentiation 19), B-Lymphocyte Surface Antigen B4, T-Cell Surface Antigen Leu-12 and CVID3 is a transmembrane protein that in humans is encoded by the gene ''CD19''. In humans, CD19 is expressed in all B lineage cells. Contrary to some early doubts, human plasma cells do express CD19, as confirmed by others. CD19 plays two major roles in human B cells: on the one hand, it acts as an adaptor protein to recruit cytoplasmic signaling proteins to the membrane; on the other, it works within the CD19/CD21 complex to decrease the threshold for B cell receptor signaling pathways. Due to its presence on all B cells, it is a biomarker for B lymphocyte development, lymphoma diagnosis and can be utilized as a target for leukemia immunotherapies. Structure In humans, CD19 is encoded by the 7.41 kilobase ''CD19'' gene located on the short arm of chromosome 16. It contains at least fifteen exons, four that encode extrac ...
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Antibody-drug Conjugate
Antibody-drug conjugates or ADCs are a class of biopharmaceutical drugs designed as a targeted therapy for treating cancer. Unlike chemotherapy, ADCs are intended to target and kill tumor cells while sparing healthy cells. As of 2019, some 56 pharmaceutical companies were developing ADCs. ADCs are complex molecules composed of an antibody linked to a biologically active cytotoxic (anticancer) payload or drug. Antibody-drug conjugates are an example of bioconjugates and immunoconjugates. ADCs combine the targeting properties of Monoclonal antibody, monoclonal antibodies with the cancer-killing capabilities of cytotoxic drugs, designed to discriminate between healthy and diseased tissue. Mechanism of action An anticancer drug is coupled to an antibody that targets a specific tumor antigen (or protein) that, ideally, is only found in or on tumor cells. Antibodies attach themselves to the antigens on the surface of cancerous cells. The biochemical reaction that occurs upon attaching ...
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Acute Lymphoblastic Leukemia
Acute lymphoblastic leukemia (ALL) is a cancer of the lymphoid line of blood cells characterized by the development of large numbers of immature lymphocytes. Symptoms may include feeling tired, pale skin color, fever, easy bleeding or bruising, enlarged lymph nodes, or bone pain. As an acute leukemia, ALL progresses rapidly and is typically fatal within weeks or months if left untreated. In most cases, the cause is unknown. Genetic risk factors may include Down syndrome, Li-Fraumeni syndrome, or neurofibromatosis type 1. Environmental risk factors may include significant radiation exposure or prior chemotherapy. Evidence regarding electromagnetic fields or pesticides is unclear. Some hypothesize that an abnormal immune response to a common infection may be a trigger. The underlying mechanism involves multiple genetic mutations that results in rapid cell division. The excessive immature lymphocytes in the bone marrow interfere with the production of new red blood cells, whi ...
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American Medical Association
The American Medical Association (AMA) is a professional association and lobbying group of physicians and medical students. Founded in 1847, it is headquartered in Chicago, Illinois. Membership was approximately 240,000 in 2016. The AMA's stated mission is "to promote the art and science of medicine and the betterment of public health." The Association also publishes the ''Journal of the American Medical Association'' (JAMA). The AMA also publishes a list of Physician Specialty Codes which are the standard method in the U.S. for identifying physician and practice specialties. The American Medical Association is governed by a House of Delegates as well as a board of trustees in addition to executive management. The organization maintains the AMA Code of Medical Ethics, and the AMA Physician Masterfile containing data on United States Physicians. The ''Current Procedural Terminology'' coding system was first published in 1966 and is maintained by the Association. It has also publi ...
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Cytotoxic Agent
Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are an immune cell or some types of venom, e.g. from the puff adder (''Bitis arietans'') or brown recluse spider (''Loxosceles reclusa''). Cell physiology Treating cells with the cytotoxic compound can result in a variety of cell fates. 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 time or energy to activate apoptotic machinery and will not express apoptotic markers. Apoptosis is characterized by well defined cytological and molecular events including a change i ...
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Seattle Genetics
SeaGen was the world's first large scale commercial tidal stream generator. It was four times more powerful than any other tidal stream generator in the world at the time of installation. It was successfully decommissioned by SIMEC Atlantis Energy Limited in summer 2019, having exported 11.6GWh to the grid since 2008. The first SeaGen generator was installed in Strangford Narrows between Strangford and Portaferry in Northern Ireland. Strangford Lough was also the site of the first known tide mill in the world, the Nendrum Monastery mill where remains dating from 787 have been excavated. History Marine Current Turbines, the developer of SeaGen, demonstrated first prototype of tidal stream generator in 1994 with a 15 kilowatt system in Loch Linnhe, off the west coast of Scotland. In May 2003, the prototype for SeaGen, '', was installed off the coast of Lynmouth, North Devon, England. Seaflow was a single rotor turbine which generated 300 kW but was not co ...
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Diffuse Large B-cell Lymphoma
Diffuse large B-cell lymphoma (DLBCL) is a cancer of B cells, a type of lymphocyte that is responsible for producing antibody, antibodies. It is the most common form of non-Hodgkin lymphoma among adults, with an annual Incidence (epidemiology), incidence of 7–8 cases per 100,000 people per year in the US and UK. This cancer occurs primarily in older individuals, with a median age of diagnosis at ~70 years, although it can occur in young adults and, in rare cases, children. DLBCL can arise in virtually any part of the body and, depending on various factors, is often a very aggressive malignancy. The first sign of this illness is typically the observation of a rapidly growing mass or tissue infiltration that is sometimes associated with systemic B symptoms, e.g. fever, Cachexia, weight loss, and night sweats. The causes of diffuse large B-cell lymphoma are not well understood. Usually DLBCL arises from normal B cells, but it can also represent a malignant transformation of other ty ...
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Biphenotype Acute Leukemia
Biphenotypic acute leukaemia (BAL) is an uncommon type of leukemia which arises in multipotent progenitor cells which have the ability to differentiate into both myeloid and lymphoid lineages. It is a subtype of "leukemia of ambiguous lineage". The direct reasons leading to BAL are still not clear. BAL can be de novo or secondary to previous cytotoxic therapy. Many factors, such viruses, hereditary factors, and radiation, might have a relationship with BAL. BAL is hard to treat. Usually the chemotherapy is chosen according to the morphology of the blast (ALL or AML). A blood-forming stem-cell transplantation is highly recommended. About 5% of acute leukaemia cases are BAL. BAL can occur in all ages of people but occurs more in adults than in children. Signs and symptoms BAL has similar symptoms to other types of leukemia, but they are usually more serious. Symptoms caused by bone marrow damage Bruising, spotting: the reason is lack of platelets. it is very common in BAL pati ...
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R-ICE Chemotherapy
ICE in the context of chemotherapy is an acronym for one of the chemotherapy regimens, used in salvage treatment of relapsed or refractory non-Hodgkin's lymphoma and Hodgkin lymphoma. In case of CD20-positive B cell lymphoid malignancies the ICE regimen is often combined today with rituximab. This regimen is then called ICE-R or R-ICE or RICE. ICE regimen consists of: # Rituximab - an anti-CD20 monoclonal antibody, which is able to kill both normal and malignant CD20-bearing B cells; # Ifosfamide - an alkylating antineoplastic agent of the oxazafosforine group; # Carboplatin - a platinum-based antineoplastic drug, also an alkylating antineoplastic agent; # Etoposide - a topoisomerase inhibitor. Dosing regimen Cycles are repeated every 14 days for 3 cycles, then high-dose chemotherapy with autologous stem-cell transplantation Autologous stem-cell transplantation (also called autogenous, autogeneic, or autogenic stem-cell transplantation and abbreviated auto-SCT) is ...
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Antibody-drug Conjugates
Antibody-drug conjugates or ADCs are a class of biopharmaceutical drugs designed as a targeted therapy for treating cancer. Unlike chemotherapy, ADCs are intended to target and kill tumor cells while sparing healthy cells. As of 2019, some 56 pharmaceutical companies were developing ADCs. ADCs are complex molecules composed of an antibody linked to a biologically active cytotoxic (anticancer) payload or drug. Antibody-drug conjugates are an example of bioconjugates and immunoconjugates. ADCs combine the targeting properties of monoclonal antibodies with the cancer-killing capabilities of cytotoxic drugs, designed to discriminate between healthy and diseased tissue. Mechanism of action An anticancer drug is coupled to an antibody that targets a specific tumor antigen (or protein) that, ideally, is only found in or on tumor cells. Antibodies attach themselves to the antigens on the surface of cancerous cells. The biochemical reaction that occurs upon attaching triggers a signal ...
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