Immunotoxic
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Immunotoxic
An immunotoxin is an artificial protein consisting of a targeting portion linked to a toxin. When the protein binds to that cell, it is taken in through endocytosis, and the toxin kills the cell. They are used for the treatment of some kinds of cancer and a few viral infections. Design These chimeric proteins are usually made of a modified antibody or antibody fragment, attached to a fragment of a toxin. The targeting portion is composed of the Fab portion of an antibody that targets a specific cell type. The toxin is usually an AB toxin, a cytotoxic protein derived from a bacterial or plant protein, from which the natural binding domain has been removed so that the Fv directs the toxin to the antigen on the target cell. Sometimes recombinant fusion proteins containing a toxin and a growth factor are also referred to as recombinant immunotoxins, although they do not contain an antibody fragment. A more specific name for this latter kind of protein is recombinant fusion toxin. ...
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Immunopharmacology And Immunotoxicology
''Immunopharmacology and Immunotoxicology'' is a bimonthly Peer review, peer-reviewed medical journal that covers preclinical and clinical studies on the regulatory effects of various agents on Immunocompetence, immunocompetent cells, as well as the immunotoxin, immunotoxicity exerted by xenobiotics and drugs. Hence, the journal encompasses a broad range of pathology, pathologies (e.g. acute and chronic infections, allergy, autoimmunity, cancer, degenerative disease, degenerative disorders, inflammation, and primary and secondary Immunodeficiency, immunodeficiencies). It is published by Informa. Editor-in-chief The editor-in-chief of ''Immunopharmacology and Immunotoxicology'' is Anders Elm Pedersen, University of Copenhagen, Danmark.Website of Anders Elm Pedersen at University of Copenhagen
accessed at Apri ...
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CD22
CD22, or cluster of differentiation-22, is a molecule belonging to the SIGLEC family of lectins. It is found on the surface of mature B cells and to a lesser extent on some immature B cells. Generally speaking, CD22 is a regulatory molecule that prevents the overactivation of the immune system and the development of autoimmune diseases. CD22 is a sugar binding transmembrane protein, which specifically binds sialic acid with an immunoglobulin (Ig) domain located at its N-terminus. The presence of Ig domains makes CD22 a member of the immunoglobulin superfamily. CD22 functions as an inhibitory receptor for B cell receptor (BCR) signaling. It is also involved in the B cell trafficking to Peyer's patches in mice. In mice, it has been shown that CD22 blockade restores homeostatic microglial phagocytosis in aging brains. Structure CD22 is a transmembrane protein with a molecular weight of 140 kDa. The extracellular part of CD22 consists of seven immunoglobulin domains and the int ...
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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 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 in ...
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Anti-CD22 Immunotoxins
An anti-CD22 immunotoxin is a monoclonal antibody (targeting CD22) linked to a cytotoxic agent. They are being studied in the treatment of some types of B-cell cancer. They bind to CD22, a receptor protein on the surface of normal B cells and B-cell tumors, and, upon internalization, kill the cells. Therapeutic immunotoxins that use Pseudomonas exotoxin As of August 2009, several anti-CD22 immunotoxins are undergoing clinical trials. CAT-3888 and CAT-8015 CAT-3888 (or BL22) is an anti-CD22 immunotoxin and completed a Phase I clinical (human) trial for the treatment of hairy cell leukemia at the NIH in the U.S. Technically, CAT-3888 is an anti-CD22 immunotoxin fusion protein between a murine anti-CD22 disulfide-linked Fv (dsFv) antibody fragment and an edited copy of bacterial Pseudomonas exotoxin PE38. The toxin is activated intracellularly, by the low pH of the lysosome into which the entire protein was internalized via the CD22 receptor. The toxin kills the targeted cell ...
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Melanoma
Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye (uveal melanoma). In women, they most commonly occur on the legs, while in men, they most commonly occur on the back. About 25% of melanomas develop from moles. Changes in a mole that can indicate melanoma include an increase in size, irregular edges, change in color, itchiness, or skin breakdown. The primary cause of melanoma is ultraviolet light (UV) exposure in those with low levels of the skin pigment melanin. The UV light may be from the sun or other sources, such as tanning devices. Those with many moles, a history of affected family members, and poor immune function are at greater risk. A number of rare genetic conditions, such as xeroderma pigmentosum, also increase the risk. Diagnosis is by biopsy and analysis of any skin lesio ...
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Cutaneous T-cell Lymphoma
Cutaneous T-cell lymphoma (CTCL) is a class of non-Hodgkin lymphoma, which is a type of cancer of the immune system. Unlike most non-Hodgkin lymphomas (which are generally B-cell-related), CTCL is caused by a mutation of T cells. The cancerous T cells in the body initially migrate to the skin, causing various lesions to appear. These lesions change shape as the disease progresses, typically beginning as what appears to be a rash which can be very itchy and eventually forming plaques and tumors before spreading to other parts of the body. Signs and symptoms The presentation depends if it is mycosis fungoides or Sézary syndrome, the most common, though not the only types. Among the symptoms for the aforementioned types are: enlarged lymph nodes, an enlarged liver and spleen, and non-specific dermatitis. Cause The cause of CTCL is unknown. Diagnosis A point-based algorithm for the diagnosis for early forms of cutaneous T-cell lymphoma was proposed by the Internatio ...
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Denileukin Diftitox
Denileukin diftitox (trade name Ontak) was an antineoplastic agent, an engineered protein combining interleukin-2 and diphtheria toxin. Denileukin diftitox could bind to interleukin-2 receptors and introduce the diphtheria toxin into cells that express those receptors, killing the cells. In some leukemias and lymphomas, malignant cells express these receptors, so denileukin diftitox can target these. In 1999, Ontak was approved by the U.S. Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ... (FDA) for treatment of Cutaneous T-cell lymphoma (CTCL). There is some evidence tying it to vision loss, and in 2006 the FDA added a black box warning to the drug's label. In 2014, marketing of Ontak was discontinued in the US. References External links ...
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Cutaneous T Cell Lymphoma
Cutaneous T-cell lymphoma (CTCL) is a class of non-Hodgkin lymphoma, which is a type of cancer of the immune system. Unlike most non-Hodgkin lymphomas (which are generally B-cell-related), CTCL is caused by a mutation of T cells. The cancerous T cells in the body initially migrate to the skin, causing various lesions to appear. These lesions change shape as the disease progresses, typically beginning as what appears to be a rash which can be very itchy and eventually forming plaques and tumors before spreading to other parts of the body. Signs and symptoms The presentation depends if it is mycosis fungoides or Sézary syndrome, the most common, though not the only types. Among the symptoms for the aforementioned types are: enlarged lymph nodes, an enlarged liver and spleen, and non-specific dermatitis. Cause The cause of CTCL is unknown. Diagnosis A point-based algorithm for the diagnosis for early forms of cutaneous T-cell lymphoma was proposed by the International Socie ...
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Resimmune
Resimmune or A-dmDT390-bisFv(UCHT1) is an experimental drug — an anti-T cell immunotoxin — that is being investigated for treatment of blood cancers such as cutaneous T cell lymphoma (CTCL). It was developed by Doctors Neville, Woo, and Liu while at the National Institutes of Health (NIH) and is under exclusive license to Angimmune, LLC. The therapy has potential applications for lymphomas and T cell driven autoimmune diseases, including multiple sclerosis, and graft-versus-host disease following stem cell or bone marrow transplant. Clinical trials Since 2009, Resimmune is being tested against cutaneous T cell lymphoma, and is in a Phase II trial: Immunotoxin Therapy for Patients With T-cell Diseases. All patients had failed at least one conventional therapy. In the Phase I portion of the trail, a subgroup of nine patients was identified with an 89% response rate. This subgroup was Stage IB-IIB with mSWAT scores of less than 50. The complete response rate was 50% (t ...
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HA22
Moxetumomab pasudotox, sold under the brand name Lumoxiti, is an anti-CD22 immunotoxin medication for the treatment of adults with relapsed or refractory hairy cell leukemia (HCL) who have received at least two prior systemic therapies, including treatment with a purine nucleoside analog. Moxetumomab pasudotox is a CD22-directed cytotoxin and is the first of this type of treatment for adults with HCL. The drug consists of the binding fragment (Fv) of an anti-CD22 antibody fused to a toxin called PE38. This toxin is a 38 kDa fragment of Pseudomonas exotoxin A. Hairy cell leukemia (HCL) is a rare, slow-growing cancer of the blood in which the bone marrow makes too many B cells (lymphocytes), a type of white blood cell that fights infection. HCL is named after these extra B cells which look “hairy” when viewed under a microscope. As the number of leukemia cells increases, fewer healthy white blood cells, red blood cells and platelets are produced. Medical uses Moxetumomab pasu ...
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Toxin
A toxin is a naturally occurring organic poison produced by metabolic activities of living cells or organisms. Toxins occur especially as a protein or conjugated protein. The term toxin was first used by organic chemist Ludwig Brieger (1849–1919) and is derived from the word toxic. Toxins can be small molecules, peptides, or proteins that are capable of causing disease on contact with or absorption by body tissues interacting with biological macromolecules such as enzymes or cellular receptors. Toxins vary greatly in their toxicity, ranging from usually minor (such as a bee sting) to potentially fatal even at extremely low doses (such as botulinum toxin). Toxins are largely secondary metabolites, which are organic compounds that are not directly involved in an organism's growth, development, or reproduction, instead often aiding it in matters of defense. Terminology Toxins are often distinguished from other chemical agents strictly based on their biological origin. ...
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Endocytosis
Endocytosis is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a vesicle containing the ingested material. Endocytosis includes pinocytosis (cell drinking) and phagocytosis (cell eating). It is a form of active transport. History The term was proposed by De Duve in 1963. Phagocytosis was discovered by Élie Metchnikoff in 1882. Pathways Endocytosis pathways can be subdivided into four categories: namely, receptor-mediated endocytosis (also known as clathrin-mediated endocytosis), caveolae, pinocytosis, and phagocytosis. * Clathrin-mediated endocytosis is mediated by the production of small (approx. 100 nm in diameter) vesicles that have a morphologically characteristic coat made up of the cytosolic protein clathrin. Clathrin-coated vesicles (CCVs) are found in virtually all cells and form domains of the plasma membrane ter ...
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