Ibritumomab
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Ibritumomab
Ibritumomab tiuxetan (pronounced ), sold under the trade name Zevalin, is a monoclonal antibody radioimmunotherapy treatment for non-Hodgkin's lymphoma. The drug uses the monoclonal mouse IgG1 antibody ibritumomab in conjunction with the chelator tiuxetan, to which a radioactive isotope (either yttrium-90 or indium-111) is added. Tiuxetan is a modified version of DTPA whose carbon backbone contains an isothiocyanatobenzyl and a methyl group. Medical use Ibritumomab is used to treat relapsed or refractory, low grade or transformed B cell non-Hodgkin's lymphoma (NHL), a lymphoproliferative disorder, and previously untreated follicular NHL in adult patients who achieve a partial or complete response to first-line chemotherapy. The treatment should not be administered to patients with ≥25% lymphoma marrow involvement and/or impaired bone marrow reserve. The treatment starts with an infusions of rituximab. This may be followed by an administration of indium-111 labelled ibritumomab ...
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Radioimmunotherapy
Radioimmunotherapy (RIT) uses an antibody labeled with a radionuclide to deliver cytotoxic radiation to a target cell. It is a form of unsealed source radiotherapy. In cancer therapy, an antibody with specificity for a tumor-associated antigen is used to deliver a lethal dose of radiation to the tumor cells. The ability for the antibody to specifically bind to a tumor-associated antigen increases the dose delivered to the tumor cells while decreasing the dose to normal tissues. By its nature, RIT requires a tumor cell to express an antigen that is unique to the neoplasm or is not accessible in normal cells. History of available agents 131I tositumomab and 90Y ibritumomab tiuxetan were the first agents of radioimmunotherapy, and they were approved for the treatment of refractory non-Hodgkin's lymphoma. This means they are used in patients whose lymphoma is refractory to conventional chemotherapy and the monoclonal antibody rituximab. Agents in clinical development A s ...
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Indium-111
Indium-111 (111In) is a radioactive isotope of indium (In). It decays by electron capture to stable cadmium-111 with a half-life of 2.8 days. Indium-111 chloride (111InCl) solution is produced by proton irradiation of a cadmium target (112Cd(p,2n) or 111Cd(p,n)) in a cyclotron, as recommended by International Atomic Energy Agency (IAEA). The former method is more commonly used as it results in a high level of radionuclide purity. Indium-111 is commonly used in nuclear medicine diagnostic imaging by radiolabeling targeted molecules or cells. During its radioactive decay, it emits low energy gamma (γ) photons which can be imaged using planar or single-photon emission computed tomography (SPECT) gamma cameras (primary energies (ε) of 171.3 keV (91%) and 245.4 keV (94%)) Uses in nuclear medicine When formulated as an 111InCl solution, it can be used to bind antibodies, peptides, or other molecular targeted proteins or other molecules, typically using a chelate to bind ...
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CD20
B-lymphocyte antigen CD20 or CD20 is expressed on the surface of all B-cells beginning at the pro-B phase (CD45R+, CD117+) and progressively increasing in concentration until maturity. In humans CD20 is encoded by the ''MS4A1'' gene. This gene encodes a member of the membrane-spanning 4A gene family. Members of this nascent protein family are characterized by common structural features and similar intron/exon splice boundaries and display unique expression patterns among hematopoietic cells and nonlymphoid tissues. This gene encodes a B-lymphocyte surface molecule that plays a role in the development and differentiation of B-cells into plasma cells. This family member is localized to 11q12, among a cluster of family members. Alternative splicing of this gene results in two transcript variants that encode the same protein. Function The protein has no known natural Ligand (biochemistry), ligand and its function is to enable optimal B-cell immune response, specifically against T-i ...
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Gamma Camera
A gamma camera (γ-camera), also called a scintillation camera or Anger camera, is a device used to image gamma radiation emitting radioisotopes, a technique known as scintigraphy. The applications of scintigraphy include early drug development and nuclear medical imaging to view and analyse images of the human body or the distribution of medically injected, inhaled, or ingested radionuclides emitting gamma rays. Imaging techniques Scintigraphy ("scint") is the use of gamma cameras to capture emitted radiation from internal radioisotopes to create two-dimensional images. SPECT (single photon emission computed tomography) imaging, as used in nuclear cardiac stress testing, is performed using gamma cameras. Usually one, two or three detectors or heads, are slowly rotated around the patient's torso. Multi-headed gamma cameras can also be used for positron emission tomography (PET) scanning, provided that their hardware and software can be configured to detect "coincidences" (nea ...
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Biogen Idec
Biogen Inc. is an American multinational biotechnology company based in Cambridge, Massachusetts, specializing in the discovery, development, and delivery of therapies for the treatment of neurological diseases to patients worldwide. History Biogen was founded in 1978 in Geneva as ''Biotechnology Geneva'' by several prominent biologists, including Kenneth Murray from the University of Edinburgh, Phillip Allen Sharp from the Massachusetts Institute of Technology, Walter Gilbert from Harvard University (Gilbert served as CEO during the start-up phase of Biogen), Heinz Schaller from the University of Heidelberg, and Charles Weissmann from the University of Zurich (Weissmann contributed the first product interferon alpha).Werner Grundlehner''Zürcher Antikörper gegen Alzheimer hat Milliardenpotenzial – und Gegenwind.''Neue Zürcher Zeitung, June 8, 2021. Retrieved June 8, 2021. Gilbert and Sharp were subsequently honored with Nobel Prizes: Gilbert was recognized in 1980 with th ...
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Stem Cell
In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of cell in a cell lineage. They are found in both embryonic and adult organisms, but they have slightly different properties in each. They are usually distinguished from progenitor cells, which cannot divide indefinitely, and precursor or blast cells, which are usually committed to differentiating into one cell type. In mammals, roughly 50–150 cells make up the inner cell mass during the blastocyst stage of embryonic development, around days 5–14. These have stem-cell capability. ''In vivo'', they eventually differentiate into all of the body's cell types (making them pluripotent). This process starts with the differentiation into the three germ layers – the ectoderm, mesoderm and endoderm – at the gastrulation stage. However ...
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Lymphoid
The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system, and complementary to the circulatory system. It consists of a large network of lymphatic vessels, lymph nodes, lymphatic or lymphoid organs, and lymphoid tissues. The vessels carry a clear fluid called lymph (the Latin word ''lympha'' refers to the deity of fresh water, "Lympha") back towards the heart, for re-circulation. Unlike the circulatory system that is a closed system, the lymphatic system is open. The human circulatory system processes an average of 20 litres of blood per day through capillary filtration, which removes plasma from the blood. Roughly 17 litres of the filtered blood is reabsorbed directly into the blood vessels, while the remaining three litres are left in the interstitial fluid. One of the main functions of the lymphatic system is to provide an accessory return route to the blood for the surplus three litres. The other main function is that of i ...
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Apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, DNA fragmentation, and mRNA decay. The average adult human loses between 50 and 70 billion cells each day due to apoptosis. For an average human child between eight and fourteen years old, approximately twenty to thirty billion cells die per day. In contrast to necrosis, which is a form of traumatic cell death that results from acute cellular injury, apoptosis is a highly regulated and controlled process that confers advantages during an organism's life cycle. For example, the separation of fingers and toes in a developing human embryo occurs because cells between the digits undergo apoptosis. Unlike necrosis, apoptosis produces cell fragments called apoptotic ...
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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: * ''Radi ...
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Antibody-dependent Cell-mediated 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 ...
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Beta Radiation
A beta particle, also called beta ray or beta radiation (symbol β), is a high-energy, high-speed electron or positron emitted by the radioactive decay of an atomic nucleus during the process of beta decay. There are two forms of beta decay, β− decay and β+ decay, which produce electrons and positrons respectively. Beta particles with an energy of 0.5 MeV have a range of about one metre in air; the distance is dependent on the particle energy. Beta particles are a type of ionizing radiation and for radiation protection purposes are regarded as being more ionising than gamma rays, but less ionising than alpha particles. The higher the ionising effect, the greater the damage to living tissue, but also the lower the penetrating power of the radiation. Beta decay modes β− decay (electron emission) An unstable atomic nucleus with an excess of neutrons may undergo β− decay, where a neutron is converted into a proton, an electron, and an electron antineutrino (the antip ...
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Isotope
Isotopes are two or more types of atoms that have the same atomic number (number of protons in their nuclei) and position in the periodic table (and hence belong to the same chemical element), and that differ in nucleon numbers (mass numbers) due to different numbers of neutrons in their nuclei. While all isotopes of a given element have almost the same chemical properties, they have different atomic masses and physical properties. The term isotope is formed from the Greek roots isos ( ἴσος "equal") and topos ( τόπος "place"), meaning "the same place"; thus, the meaning behind the name is that different isotopes of a single element occupy the same position on the periodic table. It was coined by Scottish doctor and writer Margaret Todd in 1913 in a suggestion to the British chemist Frederick Soddy. The number of protons within the atom's nucleus is called its atomic number and is equal to the number of electrons in the neutral (non-ionized) atom. Each atomic numbe ...
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