Monoclonal antibodies


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Related to Monoclonal antibodies: Polyclonal antibodies

Monoclonal antibodies

Antibody proteins that bind to a specific target molecule (antigen) at one specific site (antigenic site). In response to either infection of immunization with a foreign agent, the immune system generates many different antibodies that bind to the foreign molecules. Individual antibodies within this polyclonal antibody pool bind to specific sites on a target molecule known as epitopes. Isolation of an individual antibody within the polyclonal antibody pool would allow biochemical and biological characterization of a highly specific molecular entity targeting only a single epitope. Realization of the therapeutic potential of such specificity launched research into the development of methods to isolate and continuously generate a supply of a single lineage of antibody, a monoclonal antibody (mAb).

In 1974, W. Köhler and C. Milstein developed a process for the generation of monoclonal antibodies. In their process, fusion of an individual B cell (or B lymphocyte), which produces an antibody with a single specificity but has a finite life span, with a myeloma (B cell tumor) cell, which can be grown indefinitely in culture, results in a hybridoma cell. This hybridoma retains desirable characteristics of both parental cells, producing an antibody of a single specificity that can grow in culture indefinitely.

Generation of monoclonal antibodies through the hybridoma process worked well with B cells from rodents but not with B cells from humans. Consequently, the majority of the first monoclonal antibodies were from mice. When administered into humans as therapeutic agents in experimental tests, the human immune system recognized the mouse monoclonal antibodies as foreign agents, causing an immune response, which was sometimes severe. Although encouraging improvements in disease were sometimes seen, this response made murine (mouse) antibodies unacceptable for use in humans with a functional immune system.

Fueled by advances in molecular biology and genetic engineering in the late 1980s, efforts to engineer new generations of monoclonal antibodies with reduced human immunogenicity have come to fruition. Today there are a number of clonal antibodies approved for human therapeutic use in the United States.

Characterization of the structure of antibodies and their genes laid the foundation for antibody engineering. In most mammals, each antibody is composed of two different polypeptides, the immunoglobulin heavy chain (IgH) and the immunoglobulin light chain (IgL). Comparison of the protein sequences of either heavy of light antibody chain reveals a portion that typically varies from one antibody to the next, the variable region, and a portion that is conserved, the constant region. A heavy and a light chain are folded together in an antibody to align their respective variable and constant regions. The unique shape of the cofolded heavy- and light-chain variable domains creates the variable domain of the antibody, which fits around the shape of the target epitope and confers the binding specificity of the antibody.

Mice genetically engineered to produce fully human antibodies allow the use of established hybridoma technology to generate fully human antibodies directly, without the need for additional engineering. These transgenic mice contain a large portion of human DNA encoding the antibody heavy and light chains. Inactivation of the mouse's own heavy- and light-chain genes forces the mouse to use the human genes to make antibodies. Current versions of these mice generate a diverse polyclonal antibody response, thereby enabling the generation and recovery of optimal monoclonal antibodies using hybridoma technology.

Disease areas that currently are especially amenable to antibody-based treatments include cancer, immune dysregulation, and infection. Depending upon the disease and the biology of the target, therapeutic monoclonal antibodies can have different mechanisms of action. A therapeutic monoclonal antibody may bind and neutralize the normal function of a target. For example, a monoclonal antibody that blocks the activity of the of protein needed for the survival of a cancer cell causes the cell's death. Another therapeutic monoclonal antibody may bind and activate the normal function of a target. For example, a monoclonal antibody can bind to a protein on a cell and trigger an apoptosis signal. Finally, if a monoclonal antibody binds to a target expressed only on diseased tissue, conjugation of a toxic payload (effective agent), such as a chemotherapeutic or radioactive agent, to the monoclonal antibody can create a guided missile for specific delivery of the toxic payload to the diseased tissue, reducing harm to healthy tissue. See Antibody, Antigen, Genetic engineering, Immunology

References in periodicals archive ?
With the presence of several major players, the global anti-CD20 monoclonal antibodies (mABs) market is fragmented.
Therefore, researchers have focused on the evaluation of the different vector-design strategies for the transient and stable expression of monoclonal antibodies. It has been revealed that the LC:HC ratio can affect antibody assembly in the endoplasmic reticulum (ER).
A bioreactor is a tank which has a highly controlled environment to ensure the growth of the mammalian cells and production of the monoclonal antibodies. Rule of thumb is that it will take approximately 14 days for each batch cycle.
"No one knows the right dose" of the monoclonal antibodies, says Herold.
Monoclonal antibodies CD45, CD3, CD8, and CD45RA, all labeled with fluorescein, were purchased from BD Immunocytometry Systems (San Jose, CA).
In another lasting contribution, Herzenberg recognized that neither the FACS nor monoclonal antibodies would be useful for basic research or clinical applications unless both the instruments and the reagents were produced commercially by companies capable of scaling up to meet demand.
It is also known that monoclonal antibodies can be made from these people.
The development of specific monoclonal antibodies that target the oligodendrocytes, the cells that make and maintain myelin, raises the possibility of an effective remyelination therapy Scientists had previously observed that a variety of diseases, including MS, respond to treatment with immunoglobulin-G, which regulates the immune system and seems to play a part in spurring regrowth of myelin.
Cells that produce monoclonal antibodies specific to chicken fat cells were identified in the laboratory and six antibodies that bind only to fat cells were isolated.
The goal of the collaboration is to develop human monoclonal antibodies that neutralize factors involved in the pathogenesis of kidney fribrosis leading to end-stage renal disease and chronic transplant rejection.
Conversely, monoclonal antibodies are produced by cell colonies that result from an individual lymphocyte, hence the term monoclonal.
Called monoclonal antibodies, the probes seek out and bind to residues from a type of drug used to treat farm animals.

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