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Encyclopedia > Monoclonal antibody

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. 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. Schematic of antibody binding to an antigen An antibody is a 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. ... As a word, clone was first coined by J.B.S. Haldane as subject for theoretical replication of a frog, though the term clone is derived from κλων, the Greek word for twig. In horticulture, the spelling clon was used until the twentieth century. ... Biochemistry is the chemistry of life. ... Molecular biology is the study of biology at a molecular level. ... Medicine on the Web NLM (National Library of Medicine, contains resources for patients and healthcare professionals) Virtual Hospital (digital health sciences library by the University of Iowa) Online Medical Dictionary Collection of links to free medical resources Categories: Medicine | Health ...

Contents


Production

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 bind to 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 of the antigen. This mixture of antibodies is known as polyclonal antibodies. An antigen is a molecule that stimulates the production of antibodies. ... Typical classes Petromyzontidae (lampreys) Placodermi - extinct Chondrichthyes (cartilaginous fish) Acanthodii - extinct Actinopterygii (ray-finned fish) Actinistia (coelacanths) Dipnoi (lungfish) Amphibia (amphibians) Reptilia (reptiles) Aves (birds) Mammalia (mammals) Vertebrata is a subphylum of chordates, specifically, those with backbones or spinal columns. ... Binomial name Mus musculus Linnaeus, 1758 Mus musculus is the common house mouse. ... Binomial name Homo sapiens Linnaeus, 1758 Subspecies Homo sapiens idaltu (extinct) Homo sapiens sapiens Human beings define themselves in biological, social, and spiritual terms. ... The immune system is the organ system that protects an organism from outside biological influences. ... B cells are lymphocytes that play a large role in the humoral immune response (as opposed to the cell-mediated immune response). ... Plasma cells are B lymphocytes that secrete immunoglobulins (antibodies). ... Polyclonal antibodies are antibodies that are derived from different cell lines. ...


To produce monoclonal antibodies, one removes B-cells from the spleen of an animal that has been challenged with the antigen. These B-cells are then fused with myeloma tumor cells that can grow indefinitely in culture (myeloma is a B-cell cancer). This fusion is done by making the cell membranes more permeable. The fused hybrid cells (called hybridomas) will multiply rapidly and indefinitely (since they are cancer cells after all) and will produce large amounts of antibodies. The hybridomas are sufficiently diluted and grown, thus obtaining a number of different colonies, each producing only one type of antibody. The antibodies from the different colonies are then tested for their ability to bind to the antigen (for example with a test such as ELISA), and the most effective one is picked out. The spleen is a ductless, vertebrate gland that is not necessary for life but is closely associated with the circulatory system, where it functions in the destruction of old red blood cells and removal of other debris from the bloodstream, and also in holding a reservoir of blood. ... 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. ... See the article about cancer for the main article about malignant tumors. ... Drawing of a cell membrane A component of every biological cell, the selectively permeable cell membrane (or plasma membrane or plasmalemma) is a thin and structured bilayer of phospholipid and protein molecules that envelopes the cell. ... Pearl Days Elisa Toffoli, or Elisa, is considered one of the most beautiful and skillful voices of Italian music. ...


Monoclonal antibodies can be produced in cell culture or in 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. Binomial name Mus musculus Linnaeus, 1758 Mus musculus is the common house mouse. ... In higher vertebrates, the peritoneum is the membrane that forms the lining of the abdominal cavity - it covers most of the intra-abdominal organs. ...


In the above process, myeloma cell lines are used that have lost their ability to produce their own antibodies, so as to not dilute the target antibody. Furthermore, one uses 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). Fusions between healthy B-cells and myeloma cells are 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. Ribbon diagram of the catalytically perfect enzyme TIM. Factor D enzyme crystal prevents the immune system from inappropriately running out of control. ... Hypoxanthine-guanine phosphoribosyltransferase (HPRT) is an enzyme (EC 2. ...


Applications

Once monoclonal antibodies for a given substance have been produced, they can be used to detect for the presence and quantity of this substance, for instance in a Western blot test (to detect a substance in a solution) or an immunofluorescence test (to detect a substance in a whole cell). 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 is a method in molecular biology to detect a certain protein in a sample by using antibody specific to that protein. ... Immunofluorescence is the labeling of antibodies or antigens with fluorescent dyes. ... Immunoprecipitation is the use of a specific antibody to draw the corresponding protein or antigen out of solution. ... 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. ...


In medicinal treatments, the small variation (if any) in recognizing the antigen helps to reduce side effects. However, there are drawbacks to using monoclonal antibodies as opposed to polyclonals. Each B-lymphocyte produces antibodies that are specific not to an antigen, but to an epitope of that antigen. An epitope is a small piece of the antigen to which the antibody binds. Polyclonal antibodies bind to many epitopes of a given antigen, while monoclonals bind to a single epitope. In the processing of antibodies, certain binding capabilities are degraded. If the monoclonal antibody is susceptible to such degradation, it is useless. Polyclonals will still be useful even if certain epitope-binding species are degraded. An antigen is a molecule that stimulates the production of antibodies. ... An epitope is the part of a foreign organism (or its proteins) that is being recognised by the immune system and targeted by antibodies, cytotoxic T cells or both. ...


Monoclonal antibodies for cancer treatment

One possible treatment for cancer involves monoclonal antibodies that bind only to cancer cells specific antigen and induce an immunological response on the target cancer cell. Such mAb could also be modificated 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, however with their Fc region. The picture below shows all these possibilities: When normal cells are damaged or old they undergo apoptosis; cancer cells, however, avoid apoptosis. ... An antigen is a molecule that stimulates the production of antibodies. ... A toxin, in a scientific context, is a biologically produced substance that causes injury to the health of a living thing on contact or absorption, typically by interacting with biological macromolecules such as enzymes and receptors. ... A radionuclide is an atom with an unstable nucleus. ... Cytokines are small protein molecules that are the core of communication between immune system cells, and even between these cells and cells belonging to other tissue types. ...

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. Modified from Carter P: Improving the efficacy of antibody-based cancer therapies. Nat Rev Cancer 2001;1:118-129
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. Modified from Carter P: Improving the efficacy of antibody-based cancer therapies. Nat Rev Cancer 2001;1:118-129

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, and these are rejected by the human immune system. Various approaches to overcome this problem have been tried. 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 genetically engineered mice that produce more human-like antibodies. The immune system is the organ system that protects an organism from outside biological influences. ... Orders Subclass Monotremata Monotremata Subclass Marsupialia Didelphimorphia Paucituberculata Microbiotheria Dasyuromorphia Peramelemorphia Notoryctemorphia Diprotodontia Subclass Placentalia Xenarthra Dermoptera Desmostylia Scandentia Primates Rodentia Lagomorpha Insectivora Chiroptera Pholidota Carnivora Perissodactyla Artiodactyla Cetacea Afrosoricida Macroscelidea Tubulidentata Hyracoidea Proboscidea Sirenia The mammals are the class of vertebrate animals characterized by the presence of mammary glands... Cells in culture, stained for keratin (red) and DNA (green) Cell culture is the term applied when growing cells in a synthetic environment. ... A glycoprotein is a macromolecule composed of a protein and a carbohydrate (a sugar). ...


FDA approved monoclonal antibodies

This is a list adapted from information in a 2003 Nature Medicine article[1] and organized according to indication.

Transplant rejection is a process by which the immune system of the recipient of a transplant attacks the transplanted organ or tissue. ... Daclizumab (Zenapax) is a murine-human chimaerised monoclonal antibody to the IL-2Rα receptor of T cells. ... Hoffmann-La Roche, Ltd. ... Basiliximab (Simulect) is a murine monoclonal antibody to the IL-2Rα receptor of T cells. ... Novartis is a global pharmaceutical company based in Basel, Switzerland. ... ... Abciximab (previously known as c7E3 Fab), distributed by Eli Lilly under the trade name ReoPro®, is a platelet aggregation inhibitor mainly used during and after coronary artery procedures like angioplasty to prevent platelets from sticking together and causing thrombus (blood clot) formation within the coronary artery. ... When normal cells are damaged or old they undergo apoptosis; cancer cells, however, avoid apoptosis. ... Rituximab, sold under the trade names Rituxan and Mabthera, is a monoclonal antibody used in the treatment of B cell Non-Hodgkins lymphoma, a kind of cancer. ... Trastuzumab (Herceptin®) is an anti-cancer therapy that acts on the erbB2 receptor. ... Cetuximab (Erbitux®) is a chimeric monoclonal antibody given by intravenous injection for treatment of colorectal cancer. ... Bevacizumab is an anti-angiogenesis drug used in treatment of cancer. ... Infection is also the title of an episode of the television series Babylon 5; see Infection (Babylon 5). ... Infliximab (Remicade®) is a powerful drug used to treat auto-immune disorders like Crohns disease and rheumatoid arthritis. ...

Discovery

The idea of a "magic bullet" was first proposed by Paul Ehrlich who at the beginning of the 20th century figured 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 (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. This was used to study the structure of antibodies, but it was not possible to produce identical antibodies specific to a given antigen. 1970 was a common year starting on Thursday. ... 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. ...


The process of producing monoclonal antibodies described above was invented by Georges Köhler and César Milstein in 1975[5]; 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. César Milstein (October 8, 1927 – March 24, 2002), a British scientist, was born in Bahia Blanca, Argentina. ... 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 the 1980s Greg Winter pioneered the techniques to humanise monoclonal antibodies, while in the 1990s he began work on domain antibodies. This article needs to be wikified. ...


References

note for drug-related information sites: please take into account warnings on pages that might indicate "for US audiences only" or some other "intended audience"

  1. ^  Waldmann, Thomas A. (2003). Immunotherapy: past, present and future. Nature Medicine 9, 269-277.
  2. ^  ORTHOCLONE OKT®3 Information page at Ortho Biotech. Retrieved 2005-03-10.
  3. ^  ZENAPAX ® (daclizumab) Information page at Roche Pharmaceuticals. Retrieved 2005-03-10.
  4. ^  Novartis product page for Simulect (basiliximab for injection) . Retrieved 2005-03-09.
  5. ^  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.

  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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