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Immunotoxins
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. ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Toxin
A toxin is a naturally occurring poison produced by metabolic activities of living cells or organisms. They occur especially as proteins, often conjugated. The term was first used by organic chemist Ludwig Brieger (1849–1919), derived from '' 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. They 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). Terminology Toxins are often distinguished from other chemical agents strictly based on their biological origin. Less strict understandings embrace naturally occurring inorganic toxins, such as arsenic. Other understandings embrace synthetic analogs of naturally occurring organic poisons as toxins, and may or may not embrace naturally oc ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 t ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Anti-CD22 Immunotoxins
An anti-CD22 immunotoxin is a monoclonal antibody targeting CD22 linked to a cytotoxic agent. As of August 2009, it was studied in the treatment of some types of B-cell cancer. It binds to CD22, a receptor protein on the surface of normal B cells and B-cell tumors, and, upon internalization, kills the cells, acting as immunotoxin. 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 in 2015 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 recept ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Melanoma
Melanoma is the most dangerous type of skin cancer; it develops from the melanin-producing cells known as melanocytes. It typically occurs in the skin, but may rarely occur in the mouth, intestines, or eye (uveal melanoma). In very rare cases melanoma can also happen in the lung which is known as primary pulmonary melanoma and only happens in 0.01% of primary lung tumors. In women, melanomas most commonly occur on the legs; while in men, on the back. Melanoma is frequently referred to as malignant melanoma. However, the medical community stresses that there is no such thing as a 'benign melanoma' and recommends that the term 'malignant melanoma' should be avoided as redundant. About 25% of melanomas develop from nevus, moles. Changes in a mole that can indicate melanoma include increaseespecially rapid increasein size, irregular edges, change in color, itchiness, or nevus#Classification, skin breakdown. The primary cause of melanoma is ultraviolet light (UV) exposure in th ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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, B-cell-related), CTCL is caused by a mutation of T cells. The malignant, cancerous T cells in the body initially migrate to the human skin, 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 metastasis, 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: lymphadenopathy, enlarged lymph nodes, an hepatosplenomegaly, enlarged liver and spleen, and non-specific dermatitis. Cause The cause of CTCL remains largely unknown, but several external risk factors have been prop ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Denileukin Diftitox
Denileukin diftitox, sold under the brand name Ontak among others, is an anti-cancer medication used for the treatment of adults with T-cell lymphoma. It is an IL2-receptor-directed cytotoxin. It is an engineered protein combining interleukin-2 and diphtheria toxin. Medical uses Denileukin diftitox is indicated for the treatment of adults with relapsed or refractory stage I-III cutaneous T-cell lymphoma after at least one prior systemic therapy. Adverse effects The prescription label contains a boxed warning that capillary leak syndrome (CLS), including life-threatening or fatal reactions, can occur in people receiving denileukin diftitox. Society and culture Legal status In 1999, denileukin diftitox was approved by the US Food and Drug Administration (FDA) for the treatment of 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 g ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 remains largely unknown, but several external risk factors have been proposed as potential triggers and promoters of the disease. These include the u ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Resimmune
Resimmune or A-dmDT390-bisFv(UCHT1) is an experimental drug — an anti-T cell immunotoxin — that is being investigated for the 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% (two o ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 p ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Hairy Cell Leukemia
Hairy cell leukemia is an uncommon hematological malignancy characterized by an accumulation of abnormal B lymphocytes. The incidence of hairy cell leukemia (HCL) is 0.28-0.30 cases per 100,000 people in Europe and the United States and the prevalence is 3 cases per 100,000 in Europe with a lower prevalence in Asia, Africa and the Middle East. HCL has an indolent course but with frequent relapses, but with treatment life expectancy is usually the same as that for the general population. HCL was originally described as histiocytic leukemia, malignant reticulosis, or lymphoid myelofibrosis in publications dating back to the 1920s. The disease was formally named leukemic reticuloendotheliosis, and its characterization was significantly advanced by Bertha Bouroncle and colleagues at the Ohio State University College of Medicine in 1958. Its common name, which was coined in 1966, is derived from the "hairy" appearance of the cytoplasmic projections from malignant B cells under a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Endocytosis
Endocytosis is a cellular process in which Chemical substance, 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 (biology and chemistry), vesicle containing the ingested materials. Endocytosis includes pinocytosis (cell drinking) and phagocytosis (cell eating). It is a form of active transport. History The term was proposed by Christian de Duve, 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 vir ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
