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Cantuzumab Mertansine
Cantuzumab mertansine (SB-408075; huC242-DM1) is an antibody-drug conjugate investigated to treat colorectal cancer and other types of cancer. It is a humanized monoclonal antibody, cantuzumab (huC242) linked to a cytotoxic agent, mertansine (DM1). It was developed by ImmunoGen. Mechanism After the huC242 mab binds to the external domain of CanAg, the cantuzumab mertansine-CanAg complex is internalized, and the DM1 molecules are released intracellularly by cleavage of the DM1-huC242 disulfide bond In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. In ...s. Clinical trials Three phase I clinical studies had reported results by 2003. By 2005, clinical development had been suspended. See also * Cantuzumab ravtansine References Antibody-drug conjugates Monoclonal antibodies for ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
MUC1
Mucin short variant S1, also called polymorphic epithelial mucin (PEM) or epithelial membrane antigen (EMA), is a mucin encoded by the ''MUC1'' gene in humans. Mucin short variant S1 is a glycoprotein with extensive O-linked glycosylation of its extracellular domain. Mucins line the apical surface of epithelial cells in the lungs, stomach, intestines, eyes and several other organs. Mucins protect the body from infection by pathogen binding to oligosaccharides in the extracellular domain, preventing the pathogen from reaching the cell surface. Overexpression of MUC1 is often associated with colon, breast, ovarian, lung and pancreatic cancers. Joyce Taylor-Papadimitriou identified and characterised the antigen during her work with breast and ovarian tumors. Structure MUC1 is a member of the mucin family and encodes a membrane bound, glycosylated phosphoprotein. MUC1 has a core protein mass of 120-225 kDa which increases to 250-500 kDa with glycosylation. It extends 200-500 n ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Colorectal Cancer
Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel movements, weight loss, and fatigue. Most colorectal cancers are due to old age and lifestyle factors, with only a small number of cases due to underlying genetic disorders. Risk factors include diet, obesity, smoking, and lack of physical activity. Dietary factors that increase the risk include red meat, processed meat, and alcohol. Another risk factor is inflammatory bowel disease, which includes Crohn's disease and ulcerative colitis. Some of the inherited genetic disorders that can cause colorectal cancer include familial adenomatous polyposis and hereditary non-polyposis colon cancer; however, these represent less than 5% of cases. It typically starts as a benign tumor, often in the form of a polyp, which over time becomes cancerous. ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Humanized Monoclonal Antibody
Humanized antibodies are antibodies from non-human species whose protein sequences have been modified to increase their similarity to antibody variants produced naturally in humans. The process of "humanization" is usually applied to monoclonal antibodies developed for administration to humans (for example, antibodies developed as anti-cancer drugs). Humanization can be necessary when the process of developing a specific antibody involves generation in a non-human immune system (such as that in mice). The protein sequences of antibodies produced in this way are partially distinct from homologous antibodies occurring naturally in humans, and are therefore potentially immunogenic when administered to human patients (see also Human anti-mouse antibody). The International Nonproprietary Names of humanized antibodies end in ''-zumab'', as in ''omalizumab'' (see Nomenclature of monoclonal antibodies). Humanized antibodies are distinct from chimeric antibodies. The latter also have thei ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cantuzumab
Cantuzumab is a monoclonal antibody designed for the treatment of cancers. Also known as huC242 it binds the CanAg antigen. It is typically linked to one of several cytotoxic agents, yielding antibody-drug conjugates : * Cantuzumab mertansine * Cantuzumab ravtansine huC242 targets CanAg "HuC242 binds to the extracellular domain of the tumor-associated carbohydrate antigen known as CanAg (a novel glycoform of MUC1 Mucin short variant S1, also called polymorphic epithelial mucin (PEM) or epithelial membrane antigen (EMA), is a mucin encoded by the ''MUC1'' gene in humans. Mucin short variant S1 is a glycoprotein with extensive O-linked glycosylation of its e ...). CanAg is strongly expressed in most pancreatic, biliary, and colorectal cancers. It is also expressed in a substantial proportion of gastric cancers (55%), uterine cancers (45%), non-small cell lung cancers (40%), and bladder cancers (40%)." References Monoclonal antibodies {{monoclonal-antibody-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Mertansine
Mertansine, also called DM1 (and #Emtansine, in some of its forms emtansine), is a thiol-containing maytansinoid that for therapeutic purposes is attached to a monoclonal antibody through reaction of the thiol group with a linker structure to create an antibody-drug conjugate (ADC). ADCs with this design include trastuzumab emtansine, lorvotuzumab mertansine, and cantuzumab mertansine. Some are still experimental; others are in regular clinical use. Mechanism of action Mertansine is a tubulin inhibitor, meaning that it inhibits the assembly of microtubules by binding to tubulin (at the rhizoxin binding site).National Cancer InstituteDefinition of Maytansine/ref> The monoclonal antibody binds specifically to a structure (usually a protein) occurring in a tumour, thus directing mertansine into this tumour. This concept is called targeted therapy. Uses and chemistry The following (experimental) drugs are antibody-drug conjugates (ADC) combining monoclonal antibodies with mertansin ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
ImmunoGen
An immunogen is any substance that generates B-cell (humoral/antibody) and/or T-cell (cellular) adaptive immune responses upon exposure to a host organism. Immunogens that generate antibodies are called antigens ("antibody-generating"). Immunogens that generate antibodies are directly bound by host antibodies and lead to the selective expansion of antigen-specific B-cells. Immunogens that generate T-cells are indirectly bound by host T-cells after processing and presentation by host antigen-presenting cells. An immunogen can be defined as a complete antigen which is composed of the macromolecular carrier and epitopes (determinants) that can induce immune response. An explicit example is a hapten. Haptens are low-molecular-weight compounds that may be bound by antibodies, but cannot elicit an immune response. Consequently, the haptens themselves are nonimmunogenic and they cannot evoke an immune response until they bind with a larger carrier immunogenic molecule. The hapten-carrie ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CanAg
Cantuzumab is a monoclonal antibody designed for the treatment of cancers. Also known as huC242 it binds the CanAg antigen. It is typically linked to one of several cytotoxic agents, yielding antibody-drug conjugates : * Cantuzumab mertansine * Cantuzumab ravtansine huC242 targets CanAg "HuC242 binds to the extracellular domain of the tumor-associated carbohydrate antigen known as CanAg (a novel glycoform of MUC1 Mucin short variant S1, also called polymorphic epithelial mucin (PEM) or epithelial membrane antigen (EMA), is a mucin encoded by the ''MUC1'' gene in humans. Mucin short variant S1 is a glycoprotein with extensive O-linked glycosylation of its e ...). CanAg is strongly expressed in most pancreatic, biliary, and colorectal cancers. It is also expressed in a substantial proportion of gastric cancers (55%), uterine cancers (45%), non-small cell lung cancers (40%), and bladder cancers (40%)." References Monoclonal antibodies {{monoclonal-antibody-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Disulfide Bond
In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. In biology, disulfide bridges formed between thiol groups in two cysteine residues are an important component of the secondary and tertiary structure of proteins. ''Persulfide'' usually refers to compounds. In inorganic chemistry disulfide usually refers to the corresponding anion (āSāSā). Organic disulfides Symmetrical disulfides are compounds of the formula . Most disulfides encountered in organo sulfur chemistry are symmetrical disulfides. Unsymmetrical disulfides (also called heterodisulfides) are compounds of the formula . They are less common in organic chemistry, but most disulfides in nature are unsymmetrical. Properties The disulfide bonds are strong, with a typical bond dissociation energy of 60 kcal/mol (251& ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cantuzumab Ravtansine
Cantuzumab ravtansine (huC242-SPDB-DM4) is an antibody-drug conjugate designed for the treatment of cancers. The humanized monoclonal antibody ''cantuzumab'' (huC242) is linked to a cytotoxic agent, ravtansine (DM4). It uses a more hindered disulfide linkage than cantuzumab mertansine. See also * Cantuzumab mertansine Cantuzumab mertansine (SB-408075; huC242-DM1) is an antibody-drug conjugate investigated to treat colorectal cancer and other types of cancer. It is a humanized monoclonal antibody, cantuzumab (huC242) linked to a cytotoxic agent, mertansine (DM ... * ImmunoGen Inc, developer of DM4 based drugs References Immunology Monoclonal antibodies Antibody-drug conjugates {{monoclonal-antibody-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
