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Encyclopedia > Monoclonal antibodies

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Monoclonal antibodies (mAb) are antibodies that are identical because they were produced by one type of immune cell and are all clones of a single parent cell. Given (almost) any substance, it is possible to create monoclonal antibodies that specifically bind to that substance; they can then serve to detect or purify that substance. This has become an important tool in biochemistry, molecular biology and medicine. When used as medications, the generic name ends in -mab (see "Nomenclature of monoclonal antibodies"). Schematic of antibody binding to an antigen An antibody or immunoglobulin is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects like bacteria and viruses. ... White Blood Cells is also the name of a White Stripes album. ... In genetics, a clone is a replica of all or part of a macromolecule (eg. ... Biochemistry is the study of the chemical processes and transformations in living organisms. ... Molecular biology is the study of biology at a molecular level. ... medicines, see medication and pharmacology. ... The nomenclature of monoclonal antibodies is a naming scheme for assigning generic, or nonproprietary, names to a group of medicines called monoclonal antibodies. ...


Discovery

The idea of a "magic bullet" was first proposed by Paul Ehrlich who at the beginning of the 20th century postulated that if a compound could be made that selectively targeted a disease-causing organism, then a toxin for that organism could be delivered along with the agent of selectivity. Paul Ehrlich Paul Ehrlich (March 14, 1854 – August 20, 1915) was a German scientist who won the 1908 Nobel Prize in Physiology or Medicine. ...


In the 1970s the B-cell cancer myeloma was known, and it was understood that these cancerous B-cells all produce a single type of antibody (a paraprotein). This was used to study the structure of antibodies, but it was not yet possible to produce identical antibodies specific to a given antigen. 1970 (MCMLXX) was a common year starting on Thursday (the link is to a full 1970 calendar). ... Multiple myeloma (also known simply as myeloma or plasma cell myeloma) is a hematological malignancy of plasma cells, the cells of the immune system that produce antibodies. ... A paraprotein is an abnormal protein in the urine or blood, most often associated with multiple myeloma. ...


The process of producing monoclonal antibodies described above was invented by Georges Köhler, César Milstein, and Niels Kaj Jerne in 1975[1]; they shared the Nobel Prize in Physiology or Medicine in 1984 for the discovery. The key idea was to use a line of myeloma cells that had lost their ability to secrete antibodies, come up with a technique to fuse these cells with healthy antibody producing B-cells, and be able to select for the successfully fused cells. Georges Jean Franz Köhler (Munich, March 17, 1946 – March 7, 1995 in Freiburg im Breisgau) was a German biologist. ... César Milstein (October 8, 1927 – March 24, 2002), an Argentine-born scientist who spent most of his life in Great Britain. ... Niels Kaj Jerne (December 23, 1911 - October 7, 1994) was a British-Danish-Swedish (English-born) immunologist. ... See also: Other events of 1975 List of years in science . ... List of Nobel Prize laureates in Physiology or Medicine from 1901 to the present day. ... See also: Other events of 1984 List of years in science . ...


In 1988 Greg Winter and his team pioneered the techniques to humanise monoclonal antibodies[2], removing the reactions that many monoclonal antibodies caused in some patients. Sir Gregory Winter is a British pioneer of therapeutic monoclonal antibodies. ...


Production

Researchers looking at slides of cultures of cells that make monoclonal antibodies. These are grown in a lab and the researchers are analyzing the products to select the most promising of them.
Researchers looking at slides of cultures of cells that make monoclonal antibodies. These are grown in a lab and the researchers are analyzing the products to select the most promising of them.
Monoclonal antibodies can be grown in unlimited quantities in the bottles shown in this picture.
Monoclonal antibodies can be grown in unlimited quantities in the bottles shown in this picture.
Technician's hand filling wells with a liquid for a research test. This test involves preparation of cultures in which hybrids are grown in large quantities to produce desired antibody. This is effected by fusing myeloma cell and mouse lymphocyte to form a hybrid cell (hybridoma).
Technician's hand filling wells with a liquid for a research test. This test involves preparation of cultures in which hybrids are grown in large quantities to produce desired antibody. This is effected by fusing myeloma cell and mouse lymphocyte to form a hybrid cell (hybridoma).
Lab technician bathing prepared slides in a solution. This technician is involved in the preparation of slides of monoclonal antibodies for researchers. These highly specific cells shown are those labeling human breast cancer.
Lab technician bathing prepared slides in a solution. This technician is involved in the preparation of slides of monoclonal antibodies for researchers. These highly specific cells shown are those labeling human breast cancer.

If a foreign substance (an antigen) is injected into a vertebrate such as a mouse or a human, some of the immune system's B-cells will turn into plasma cells and start to produce antibodies that recognize that antigen. Each B-cell produces only one kind of antibody, but different B-cells will produce structurally different antibodies that bind to different parts ("epitopes") of the antigen. This natural mixture of antibodies found in serum is known as polyclonal antibodies. Image File history File linksMetadata Download high-resolution version (1350x900, 676 KB) Public domain image from cancer. ... Image File history File linksMetadata Download high-resolution version (1350x900, 676 KB) Public domain image from cancer. ... Image File history File linksMetadata Download high-resolution version (1350x900, 623 KB) Public domain image from cancer. ... Image File history File linksMetadata Download high-resolution version (1350x900, 623 KB) Public domain image from cancer. ... Image File history File linksMetadata Download high-resolution version (1350x900, 601 KB) Public domain image from cancer. ... Image File history File linksMetadata Download high-resolution version (1350x900, 601 KB) Public domain image from cancer. ... A technician is generally someone in a technological field who has a relatively practical understanding of the general theoretical principles of that field, e. ... Multiple myeloma (also known as MM, myeloma, plasma cell myeloma, or as Kahlers disease after Otto Kahler) is a type of cancer of plasma cells which are immune system cells in bone marrow that produce antibodies. ... Binomial name Mus musculus Linnaeus, 1758 Mus musculus is the common house mouse. ... A lymphocyte is a type of white blood cell involved in the human bodys immune system. ... Monoclonal antibodies (mAb) are antibodies that are identical because they were produced by one type of immune cell, all clones of a single parent cell. ... Image File history File linksMetadata Download high-resolution version (1350x900, 451 KB) Public domain image from cancer. ... Image File history File linksMetadata Download high-resolution version (1350x900, 451 KB) Public domain image from cancer. ... Breast cancer is cancer of breast tissue. ... An antigen is a substance that stimulates an immune response, especially the production of antibodies. ... Classes and Clades See below Male and female Superb Fairy-wren Vertebrates are members of the subphylum Vertebrata (within the phylum Chordata), specifically, those chordates with backbones or spinal columns. ... Binomial name Mus musculus Linnaeus, 1758 Mus musculus is the common house mouse. ... Trinomial name Homo sapiens sapiens Linnaeus, 1758 Humans, or human beings, are bipedal primates belonging to the mammalian species Homo sapiens (Latin: wise man or knowing man) under the family Hominidae (the great apes). ... A scanning electron microscope image of a single human lymphocyte. ... B cells are lymphocytes that play a large role in the humoral immune response (as opposed to the cell-mediated immune response). ... Plasma cells (also called plasma B cells or plasmocytes) are cells of the immune system that secrete large amounts of antibodies. ... An epitope is the part of a macromolecule that is recognized by the immune system, specifically by antibodies, B cells, or cytotoxic T cells. ... Polyclonal antibodies are antibodies that are derived from different B-cell lines. ...


To produce monoclonal antibodies, one removes B-cells from the spleen or lymph nodes of an animal that has been challenged several times with the antigen of interest. These B-cells are then fused with myeloma tumor cells that can grow indefinitely in culture (myeloma is a B-cell cancer) and that have lost the ability to produce antibodies. This fusion is done by making the cell membranes more permeable by the use of polyethylene glycol, electroporation or, of historical importance, infection with some virus. The fused hybrid cells (called hybridomas), being cancer cells, will multiply rapidly and indefinitely. Large amounts of antibodies can therefore be produced. The hybridomas are sufficiently diluted to ensure clonality and grown. The antibodies from the different clones are then tested for their ability to bind to the antigen (for example with a test such as ELISA) or immuno-dot blot, and the most sensitive one is picked out. The spleen is a ductless, vertebrate gland that is closely associated with the circulatory system, where it functions in the destruction of old red blood cells in holding a reservoir of blood. ... Lymph nodes are components of the lymphatic system. ... Multiple myeloma (also known simply as myeloma or plasma cell myeloma) is a hematological malignancy of plasma cells, the cells of the immune system that produce antibodies. ... Tumor or tumour literally means swelling, and is sometimes still used with that meaning. ... Illustration of a cell membrane The cell membrane, also called the plasma membrane or plasmalemma, is a semipermeable lipid layer surrounding the cytoplasm of all living cells. ... The Enzyme-Linked ImmunoSorbent Assay, or ELISA, is a biochemical technique used mainly in immunology to detect the presence of an antibody or an antigen in a sample. ...


In the above process, one uses myeloma cell lines that have lost their ability to produce their own antibodies or antibody chain, so as to not contaminate the target antibody. Furthermore, one employs only myeloma cells that have lost a specific enzyme (hypoxanthine-guanine phosphoribosyltransferase, HGPRT) and therefore cannot grow under certain conditions (namely in the presence of HAT medium). These cells are preselected by the use of 8-azaguanine media prior to the fusion. Cells that possess the HGPRT enzyme will be killed by the 8-azaguanine. During the fusion process many cells can fuse. Myeloma with myeloma, spleen cell with spleen cell, 3 cells of different types etc... The desired fusions are between healthy B-cells producing antibodies against the antigen of interest and myeloma cells. These are relatively rare, but when one succeeds, then the healthy partner supplies the needed enzyme and the fused cell can survive in HAT medium. This is the trick to detect the successfully fused cells. The medium must be enriched during selection to favour hybridoma growth. This can be achieved by the use of a layer of feeder cells or supplement media such as briclone. Ribbon diagram of the enzyme TIM, surrounded by the space-filling model of the protein. ... Hypoxanthine-guanine phosphoribosyltransferase (HPRT) is an enzyme (EC 2. ... HAT Medium (Hypoxanthine Aminopterin Thymidine ) is a medium used for preparation of monoclonal antibodies. ... Briclone is an IL-6 enriched cloning medium for use in the stages following fusion in hybridoma production. ...


Monoclonal antibodies can be produced in cell culture or in live animals. When the hybridoma cells are injected in mice (in the peritoneal cavity, the gut), they produce tumors containing an antibody-rich fluid called ascites fluid. Production in cell culture is usually preferred as the ascites technique may be very painful to the animal and if replacement techniques exist, may be considered unethical. Fermentation chambers have been used to produce antibodies on a larger scale. Nowadays, bioengineering allow production of antibodies in plants. Epithelial cells in culture, stained for keratin (red) and DNA (green) Cell culture is the term applied when cells are grown in a synthetic environment. ... Binomial name Mus musculus Linnaeus, 1758 Mus musculus is the common house mouse. ... In higher vertebrates, the peritoneum is the serous membrane that forms the lining of the abdominal cavity - it covers most of the intra-abdominal organs. ...


Applications

Once monoclonal antibodies for a given substance have been produced, they can be used to detect the presence and quantity of this substance, for instance in a Western blot test (to detect a protein on a membrane) or an immunofluorescence test (to detect a substance in a cell). They are also very useful in immunohistochemistry which detect antigen in fixed tissue sections. Monoclonal antibodies can also be used to purify a substance with techniques called immunoprecipitation and affinity chromatography. Picture of a western blot with 5 vertical lanes A western blot (a. ... Immunofluorescence is the labeling of antibodies or antigens with fluorescent dyes. ... Immunoprecipitation is the technique of precipitating an antigen out of solution using an antibody specific to that antigen. ... Affinity chromatography is a biochemical separation method that combines size fractionation capability of gel permeation chromatography with the ability to design a stationary phase that reversibly binds to a known subset of molecules. ...


Monoclonal antibodies for cancer treatment

One possible treatment for cancer involves monoclonal antibodies that bind only to cancer cell-specific antigens and induce an immunological response against the target cancer cell. Such mAb could also be modified for delivery of a toxin, radioisotope, cytokine or other active conjugate; it is also possible to design bispecific antibodies that can bind with their Fab regions both to target antigen and to a conjugate or effector cell. In fact, every intact antibody can bind to cell receptors or other proteins with its Fc region. The illustration below shows all these possibilities: Monoclonal antibody therapy is the use of monoclonal antibodies (-mab) to specifically target cells. ... Cancer is a class of diseases or disorders characterized by uncontrolled division of cells and the ability of these cells to spread, either by direct growth into adjacent tissue through invasion, or by implantation into distant sites by metastasis (where cancer cells are transported through the bloodstream or lymphatic system). ... An antigen is any molecule that is recognized by antibodies. ... The venom of the black widow spider is a potent latrotoxin. ... A radionuclide is an atom with an unstable nucleus. ... Cytokines is a group of proteinaceous signalling compounds that like hormones and neurotransmitters are used extensively for inter-cell communication. ...

Monoclonal antibodies for cancer. ADEPT, antibody directed enzyme prodrug therapy; ADCC, antibody dependent cell-mediated cytotoxicity; CDC, complement dependent cytotoxicity; MAb, monoclonal antibody; scFv, single-chain Fv fragment.
Monoclonal antibodies for cancer. ADEPT, antibody directed enzyme prodrug therapy; ADCC, antibody dependent cell-mediated cytotoxicity; CDC, complement dependent cytotoxicity; MAb, monoclonal antibody; scFv, single-chain Fv fragment. [3]

Monoclonal antibodies for cancer. ...

Chimeric and humanized antibodies

One problem in medical applications is that the standard procedure of producing monoclonal antibodies yields mouse antibodies. Although murine antibodies are very similar to human ones there are differences. The human immune system hence recognizes mouse antibodies as foreign, rapidly removing them from circulation and causing systemic inflammatory effects. A scanning electron microscope image of a single human lymphocyte. ...


A solution to this problem would be to generate human antibodies directly from humans. However, this is not easy, primarily because it is clearly not ethical to challenge humans with antigen in order to produce antibody. Furthermore, it is not easy to generate human antibodies against human tissues.


Various approaches using recombinant DNA technology to overcome this problem have been tried since the late 1980s. In one approach, one takes the DNA that encodes the binding portion of monoclonal mouse antibodies and merges it with human antibody producing DNA. One then uses mammalian cell cultures to express this DNA and produce these half-mouse and half-human antibodies. (Bacteria cannot be used for this purpose, since they cannot produce this kind of glycoprotein.) Depending on how big a part of the mouse antibody is used, one talks about chimeric antibodies or humanized antibodies. Another approach involves mice genetically engineered to produce more human-like antibodies. Monoclonal antibodies have been generated and approved to treat;cancer, cardiovascular disease, inflammatory diseases, macular degeneration, transplant rejection, and viral infection (see monoclonal antibody therapy). Subclasses Allotheria* Order Multituberculata (extinct) Order Volaticotheria (extinct) Order Palaeoryctoides (extinct) Order Triconodonta (extinct) Prototheria Order Monotremata Theria Infraclass Marsupialia Infraclass Eutheria The mammals are the class of vertebrate animals characterized by the production of milk in females for the nourishment of young, from mammary glands present on most species... Epithelial cells in culture, stained for keratin (red) and DNA (green) Cell culture is the term applied when cells are grown in a synthetic environment. ... A glycoprotein is a macromolecule composed of a protein and a carbohydrate (an oligosaccharide). ... Transgenic animals are animals produced with externally introduced genes. ... Cancer is a class of diseases or disorders characterized by uncontrolled division of cells and the ability of these cells to spread, either by direct growth into adjacent tissue through invasion, or by implantation into distant sites by metastasis (where cancer cells are transported through the bloodstream or lymphatic system). ... Cardiovascular disease refers to the class of diseases that involve the heart and/or blood vessels (arteries and veins). ... Inflammation is the first response of the immune system to infection or irritation and may be referred to as the innate cascade. ... Listen to this article · (info) This audio file was created from an article revision dated 2005-07-19, and may not reflect subsequent edits to the article. ... Transplant rejection occurs when the immune system of the recipient of a transplant attacks the transplanted organ or tissue. ... Infection is also the title of an episode of the television series Babylon 5; see Infection (Babylon 5). ... Monoclonal antibody therapy is the use of monoclonal antibodies (-mab) to specifically target cells. ...


In August 2006 the Pharmaceutical Research and Manufacturers of America reported that U.S. companies had 160 different monoclonal antibodies in clinical trials or awaiting approval by the Food and Drug Administration.[4] The Pharmaceutical Research and Manufacturers of America (PhRMA) is a trade body of the pharmaceutical industry of the United States. ... The Food and Drug Administration (FDA) is an agency of the United States Department of Health and Human Services and is responsible for regulating food (humans and animal), dietary supplements, drugs (human and animal), cosmetics, medical devices (human and animal) and radiation emitting devices (including non-medical devices), biologics, and...


See also

Monoclonal antibody therapy is the use of monoclonal antibodies (-mab) to specifically target cells. ... The nomenclature of monoclonal antibodies is a naming scheme for assigning generic, or nonproprietary, names to a group of medicines called monoclonal antibodies. ... Polyclonal antibodies are antibodies that are derived from different B-cell lines. ... Nanobodies are a type of antibodies derived from camels, and are much smaller than traditional antibodies. ...

References

  1. ^ Kohler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 1975;256:495-7. PMID 1172191. Reproduced in J Immunol 2005;174:2453-5. PMID 15728446.
  2. ^ Riechmann L, Clark M, Waldmann H, Winter G. Reshaping human antibodies for therapy. Nature 1988;332:323-7. PMID 3127726.
  3. ^ Modified from Carter P: Improving the efficacy of antibody-based cancer therapies. Nat Rev Cancer 2001;1:118-129
  4. ^ PhRMA Reports Identifies More than 400 Biotech Drugs in Development. Pharmaceutical Technology, August 24, 2006. Retrieved 2006-09-04.

First title page, November 4, 1869 Nature is one of the oldest and most reputable scientific journals, first published on 4 November 1869. ... First title page, November 4, 1869 Nature is one of the oldest and most reputable scientific journals, first published on 4 November 1869. ...

External links

  • Attana - Sample usage of antibodies (Animation)
  • Flash animation at McGraw-Hill immunology-Monoclonal%20Antibodies
  • Antibody Resource Page
  • Monoclonal Antibodies, from John W. Kimball's online biology textbook
  • Production and Quality Control of Monoclonal Antibodies; European Commission directive, July 1995

  Results from FactBites:
 
ACS :: Monoclonal Antibodies (1603 words)
Monoclonal antibody therapy is a passive immunotherapy because the antibodies are produced in large quantities outside the body (in the lab) rather than by your immune system...
Monoclonal antibody therapy is a form of passive immunotherapy because it uses antibodies made in large numbers outside the body (in the lab) rather than by a person's own immune system.
The first monoclonal antibodies were made in the lab by fusing a myeloma (a type of bone marrow cancer) cell from a mouse with a mouse B cell that makes a specific antibody.
Monoclonal Antibody Technology - The Basics (586 words)
Second, some antibodies, once activated by the occurrence of a disease, continue to confer resistance against that disease; classic examples are the antibodies to the childhood diseases chickenpox and measles.
Monoclonal antibody technology allows us to produce large amounts of pure antibodies in the following way: We can obtain cells that produce antibodies naturally; we also have available a class of cells that can grow continually in cell culture.
These antibodies are called monoclonal because they come from only one type of cell, the hybridoma cell; antibodies produced by conventional methods, on the other hand, are derived from preparations containing many kinds of cells, and hence are called polyclonal.
  More results at FactBites »

 
 

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