Synthetic antibodies
Synthetic antibodies are artificially generated proteins designed to mimic natural human antibodies, which play a crucial role in the immune response by targeting and neutralizing foreign substances, known as antigens. Developed as a response to the limitations of traditional antibody therapies derived from animal sources, synthetic antibodies offer significant advantages, including reduced risk of allergic reactions. The breakthrough in synthetic antibody technology came in 1975 with the creation of hybridoma cells, which are formed by fusing normal B cells with myeloma cells, allowing for the mass production of monoclonal antibodies.
Research in synthetic antibodies has expanded into various medical applications, such as preventing organ transplant rejection, treating drug overdoses, and offering new therapeutic options for conditions like cancer and AIDS. One notable achievement was the FDA's approval of a synthetic antibody for non-Hodgkin's lymphoma in 1997, marking a significant milestone in cancer treatment. Additionally, new techniques are being explored, including the creation of symphobodies, which combine multiple synthetic antibodies to target various antigens simultaneously, thus enhancing treatment efficacy. The ongoing advancements in synthetic antibody technology hold promise for innovative therapies in diverse medical fields, underlining their importance in both clinical and research settings.
Synthetic antibodies
SIGNIFICANCE: Synthetic antibodies are artificially produced replacements for natural human antibodies. They are used to treat a variety of illnesses and promise to continue to be an important part of medical technology in the future.
The Development of Antibody Therapy
Natural antibodies are protein molecules produced by white blood cells known as in response to the presence of foreign substances. A specific binds to a specific substance, known as an antigen, in a way that renders it harmless or allows it to be removed from the body or destroyed. A person will produce antibodies naturally upon exposure to harmless versions of an antigen, a process known as active immunization. Active immunization was the first form of antibody therapy to be developed and is used to prevent diseases such as measles and polio.
The oldest method of producing therapeutic antibodies outside the human body is known as passive immunization. This process involves exposing an animal to an antigen so that it develops antibodies to it. The antibodies are separated from the animal’s blood and administered to a patient. Passive immunization is used to treat diseases such as rabies and diphtheria. A disadvantage of antibodies derived from animal blood is the possibility that the patient may develop an allergic reaction. Because the animal’s antibodies are foreign substances, the patient’s own antibodies may treat them as antigens, leading to fever, rash, itching, joint pain, swollen tissues, and other symptoms. Antibodies derived from human blood are much less likely to cause allergic reactions than antibodies from the blood of other animals. This led researchers to seek a way to develop synthetic human antibodies.
A major breakthrough in the search for synthetic antibodies was made in 1975 by Cesar Milstein and Georges Köhler. They developed a technique that allowed them to produce a specific antibody outside the body of a living animal. This method involved exposing an animal to an antigen, causing it to produce antibodies. Instead of obtaining the antibodies from the animal’s blood, they obtained B cells from the animal’s spleen. These cells are then combined with abnormal B cells known as myeloma cells. Unlike normal B cells, myeloma cells can reproduce identical copies of themselves an unlimited number of times. The normal B cells and the myeloma cells fuse to form cells known as hybridoma cells. Hybridoma cells are able to reproduce an unlimited number of times and are able to produce the same antibodies as the B cells. Those hybridoma cells that produce the desired antibody are separated from the others and allowed to reproduce. The antibodies produced this way are known as monoclonal antibodies.
Because human B cells do not normally form stable hybridoma cells with myeloma cells, B cells from mice have been used. Because mouse antibodies are not identical to human antibodies, they may be treated as antigens by the patient’s own antibodies, leading to allergic reactions. During the 1980s and 1990s, researchers began to develop methods of producing synthetic antibodies that were similar or identical to human antibodies. An antibody consists of a variable region, which binds to the antigen, and a constant region. The risk of allergic reactions can be reduced by combining variable regions derived from mouse hybridoma cells with constant regions from human cells. The risk can be further reduced by identifying the exact sites on the mouse variable region that are necessary for binding and integrating these sites into human variable regions. This method produces synthetic antibodies that are very similar to human antibodies.
Other methods exist to produce synthetic antibodies that are identical to human antibodies. A species of virus known as the Epstein-Barr virus can be used to change human B cells in such a way that they will fuse with myeloma cells to form stable hybridoma cells that produce human antibodies. Another method involves using to produce mice with B cells that produce human antibodies rather than mouse antibodies. One of the most promising techniques has been the creation of libraries of synthetic human antibodies. This process is done by using the polymerase chain reaction (PCR) to produce multiple copies of the genetic material within B cells. This genetic material contains the information that results in the production of proteins that come together to form antibodies. By causing these proteins to be produced and allowing them to combine at random, researchers are able to produce millions of different antibodies. The antibodies are then tested to detect those that bind to selected antigens.
Impact and Applications
Some synthetic antibodies are used to help prevent the rejection of transplanted organs. An antibody that binds to the heart drug digoxin can be used to treat overdoses of that drug. Antibodies attached to radioactive isotopes are used in certain diagnostic procedures. Synthetic antibodies have also been used in patients undergoing a heart procedure known as a percutaneous transluminal coronary angioplasty (PTCA). The use of a particular synthetic antibody has been shown to reduce the risk of having one of the blood vessels that supply blood to the heart shut down during or after a PTCA. Researchers also hope to develop synthetic antibodies to treat acquired immunodeficiency syndrome (AIDS) and septic shock, a syndrome caused by toxic substances released by certain bacteria.
The most active area of research involving synthetic antibodies in the 1990s was in the treatment of cancer. On November 26, 1997, the US Food and Drug Administration approved a synthetic antibody for use in non-Hodgkin’s lymphoma, a cancer of the white blood cells. It was the first synthetic antibody approved for use in cancer therapy.
Antibodies are important for immune system protection against pathogens. They are also important tools in biological research, as with the use of antibodies to help determine the structure of cellular proteins. There may be a role for synthetic antibodies in determining the structure of RNA as well. RNA is genetic material that works with DNA. DNA is the master genetic code, but the role of RNA is a crucial one. More information on RNA structure may unveil more information on RNA function.
New approaches to therapeutic synthetic antibodies are in development. One approach involves the production of symphobodies. Symphobodies are made up of several different synthetic antibodies attacking a variety of antigens on the same target. These targets can be tumor or cancer cells or whole organisms such as viruses. Multiple synthetic antibody attacks on the same pathogen could result in more effective treatment.
Key terms
- antibodya protein molecule that binds to a substance in order to remove, destroy, or deactivate it
- antigenthe substance to which an antibody binds
- B cellswhite blood cells that produce antibodies
- monoclonal antibodiesidentical antibodies produced by identical B cells
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