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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 enginee ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Oligosaccharides
An oligosaccharide (/ˌɑlɪgoʊˈsækəˌɹaɪd/; from the Greek ὀλίγος ''olígos'', "a few", and σάκχαρ ''sácchar'', "sugar") is a saccharide polymer containing a small number (typically two to ten) of monosaccharides (simple sugars). Oligosaccharides can have many functions including cell recognition and cell adhesion. They are normally present as glycans: oligosaccharide chains are linked to lipids or to compatible amino acid side chains in proteins, by ''N''- or ''O''-glycosidic bonds. ''N''-Linked oligosaccharides are always pentasaccharides attached to asparagine via a beta linkage to the amine nitrogen of the side chain.. Alternately, ''O''-linked oligosaccharides are generally attached to threonine or serine on the alcohol group of the side chain. Not all natural oligosaccharides occur as components of glycoproteins or glycolipids. Some, such as the raffinose series, occur as storage or transport carbohydrates in plants. Others, such as maltodext ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
GnTIII
Beta-1,4-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase (, ''N-acetylglucosaminyltransferase III'', ''N-glycosyl-oligosaccharide-glycoprotein N-acetylglucosaminyltransferase III'', ''uridine diphosphoacetylglucosamine-glycopeptide beta4-acetylglucosaminyltransferase III'', ''beta-1,4-mannosyl-glycoprotein beta-1,4-N-acetylglucosaminyltransferase'', ''GnTIII'') is an enzyme with systematic name ''UDP-N-acetyl-D-glucosamine:beta-D-mannosyl-glycoprotein 4-beta-N-acetyl-D-glucosaminyltransferase''. This enzyme catalyses the following chemical reaction : UDP-N-acetyl-D-glucosamine + beta-D-mannosyl-R \rightleftharpoons UDP + 4-(N-acetyl-beta-D-glucosaminyl)-beta-D-mannosyl-R R represents the remainder of the N-linked oligosaccharide in the glycoprotein Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. Thi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Fc 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 region, con ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
FUT8
Alpha-(1,6)-fucosyltransferase is an enzyme that in humans is encoded by the ''FUT8'' gene. This enzyme belongs to the family of fucosyltransferases. The product of this gene catalyzes the transfer of fucose from GDP-fucose to N-linked type complex glycopeptides. This enzyme is distinct from other fucosyltransferases which catalyze alpha1-2, alpha1-3, and alpha1-4 fucose addition. The expression of this gene may contribute to the malignancy of cancer cells and to their invasive and metastatic capabilities. Alternatively spliced variants encoding different isoforms have been identified. Kyowa Hakko Kirin is a Japanese pharmaceutical and biotechnology company under the Kirin Holdings, and is among the 40 largest in the world by revenue. The company is headquartered in Chiyoda-ku, Tokyo and is a member of the Nikkei 225 stock index. History On ...'s "Potelligent" platform uses a CHO cell line in which ''FUT8'' has been knocked out to make afucosylated monoclonal antibodies. ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Chronic Lymphocytic Leukemia
Chronic lymphocytic leukemia (CLL) is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell). Early on, there are typically no symptoms. Later, non-painful lymph node swelling, feeling tired, fever, night sweats, or weight loss for no clear reason may occur. Enlargement of the spleen and low red blood cells (anemia) may also occur. It typically worsens gradually over years. Risk factors include having a family history of the disease, with 10% of those who develop CLL having a family history of the disease. Exposure to Agent Orange, certain insecticides, sun exposure, exposure to hepatitis C virus, and common infections are also considered risk factors. CLL results in the buildup of B cell lymphocytes in the bone marrow, lymph nodes, and blood. These cells do not function well and crowd out healthy blood cells. CLL is divided into two main types: those with a mutated IGHV gene and those without. Diagnosis is typically based o ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Obinutuzumab
Obinutuzumab, sold under the brand name Gazyva among others, is a humanized anti-CD20 monoclonal antibody, originated by GlycArt Biotechnology AG and developed by Roche as a cancer treatment. It can be used as a first-line treatment for chronic lymphocytic leukemia in combination with chemotherapy or with venetoclax, as a first-line treatment for follicular lymphoma in combination with chemotherapy, and as treatment for relapsed or refractory follicular lymphoma in combination with bendamustine chemotherapy. Medical uses Obinutuzumab is used in combination with chlorambucil as a first-line treatment for chronic lymphocytic leukemia. Its progression-free survival is significantly better than rituximab in the same combination (26.7 months vs. 15.2 months, p In January 2019, the US Food and Drug Administration (FDA) approved ibrutinib in combination with obinutuzumab for people with chronic lymphocytic leukemia/ small lymphocytic lymphoma who have not received prior treatment. Re ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
ETH Zurich
(colloquially) , former_name = eidgenössische polytechnische Schule , image = ETHZ.JPG , image_size = , established = , type = Public , budget = CHF 1.896 billion (2021) , rector = Günther Dissertori , president = Joël Mesot , academic_staff = 6,612 (including doctoral students, excluding 527 professors of all ranks, 34% female, 65% foreign nationals) (full-time equivalents 2021) , administrative_staff = 3,106 (40% female, 19% foreign nationals, full-time equivalents 2021) , students = 24,534 (headcount 2021, 33.3% female, 37% foreign nationals) , undergrad = 10,642 , postgrad = 8,299 , doctoral = 4,460 , other = 1,133 , address = Rämistrasse 101CH-8092 ZürichSwitzerland , city = Zürich , coor = , campus = Urban , language = German, English (Masters and upwards, sometimes Bachelor) , affiliations = CESAER, EUA, GlobalTech, IARU, IDEA League, UNITECH , website ethz.ch, colors = Black and White , logo = ETH Zürich Logo black.svg ETH Zür ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Hoffmann-La Roche
F. Hoffmann-La Roche AG, commonly known as Roche, is a Swiss multinational healthcare company that operates worldwide under two divisions: Pharmaceuticals and Diagnostics. Its holding company, Roche Holding AG, has shares listed on the SIX Swiss Exchange. The company headquarters are located in Basel. Roche is the fifth largest pharmaceutical company in the world by revenue, and the leading provider of cancer treatments globally. The company controls the American biotechnology company Genentech, which is a wholly owned affiliate, and the Japanese biotechnology company Chugai Pharmaceuticals, as well as the United States-based companies Ventana and Foundation Medicine. Roche's revenues during fiscal year 2020 were 58.32 billion Swiss francs. Descendants of the founding Hoffmann and Oeri families own slightly over half of the bearer shares with voting rights (a pool of family shareholders 45%, and Maja Oeri a further 5% apart), with Swiss pharma firm Novartis owning a fur ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Chinese Hamster Ovary Cell
Chinese hamster ovary (CHO) cells are an epithelial cell line derived from the ovary of the Chinese hamster, often used in biological and medical research and commercially in the production of recombinant therapeutic proteins. They have found wide use in studies of genetics, toxicity screening, nutrition and gene expression, particularly to express recombinant proteins. CHO cells are the most commonly used mammalian hosts for industrial production of recombinant protein therapeutics. History Chinese hamsters had been used in research since 1919, where they were used in place of mice for typing pneumococci. They were subsequently found to be excellent vectors for transmission of kala-azar (visceral leishmaniasis), facilitating ''Leishmania'' research. In 1948, the Chinese hamster was first used in the United States for breeding in research laboratories. In 1957, Theodore T. Puck obtained a female Chinese hamster from Dr. George Yerganian's laboratory at the Boston Cancer Research ... [...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 region, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Natural Killer Cells
Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic lymphocyte critical to the innate immune system that belong to the rapidly expanding family of known innate lymphoid cells (ILC) and represent 5–20% of all circulating lymphocytes in humans. The role of NK cells is analogous to that of cytotoxic T cells in the vertebrate adaptive immune response. NK cells provide rapid responses to virus-infected cell and other intracellular pathogens acting at around 3 days after infection, and respond to tumor formation. Typically, immune cells detect the major histocompatibility complex (MHC) presented on infected cell surfaces, triggering cytokine release, causing the death of the infected cell by lysis or apoptosis. NK cells are unique, however, as they have the ability to recognize and kill stressed cells in the absence of antibodies and MHC, allowing for a much faster immune reaction. They were named "natural killers" because of the n ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
FCGR3A
Low affinity immunoglobulin gamma Fc region receptor III-A is a protein that in humans is encoded by the ''FCGR3A'' gene. It is also known as CD16a as it is part of the cluster of differentiation The cluster of differentiation (also known as cluster of designation or classification determinant and often abbreviated as CD) is a protocol used for the identification and investigation of cell surface molecules providing targets for immunophen ... cell surface molecules. References Further reading * * * * * * * * * * * * * * * * * * * * * External links * Clusters of differentiation Fc receptors {{immunology-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
