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Monoclonal Antibodies - Mechanism, Applications and ChallengesBY: Pournami Gouthaman | Category: Biotechnology-products | Submitted: 2011-04-10 09:35:25
Monoclonal antibodies are specific antibodies produced by the clones derived from a single parent cell, by fusing the antibody-producing cell (B cell) with a laboratory cultured myeloma cell through the process of somatic cell hybridization. The result is a hybridoma which has the capability to produce mono-specific antibody that can help in the recognition or purification of a target cell. Due to its characteristic of increased specificity, these were believed to transform into a powerful tool in molecular biology, biochemistry and medicine. This dream was successfully realized when immunotherapy became a popular tool for various medical applications, especially in cancer treatment. But along with its wide spectrum of uses in targeted therapy, there were certain hurdles too, which should be overcome.
Antibodies are used for diagnostic purposes. If monoclonal antibodies against a particular substance (antigen) are produced, this can be used to detect the same. A typical example is the ELISA test for diagnosis of AIDS. Antibodies that target human chorionic gonadotropin (HCG) are used in pregnancy test kits worldwide. The presence of a particular protein on a membrane is detected by tests such as Western blot and immune dot blot. Monoclonal antibodies are also excellent candidates for immunohistochemistry and immunofluorescence test which detects antigens in fixed tissue sections, frozen tissue sections or live cells.
Monoclonal antibody therapy was a major breakthrough in medical science. Antibodies that specifically bind to target cells are used to stimulate the patient's natural immune system to fight against these cells. Various research activities are being carried out in this field because production of a monoclonal antibody which is specific to any extracellular substance is possible and this opens numerous possibilities for treatment against serious diseases like multiple sclerosis, rheumatoid arthritis and even cancer. The mechanism by which monoclonal antibodies work can be either direct or indirect. The direct therapeutic effect is carried out by producing programmed cell death or apoptosis. They have the ability to stop the proliferation of tumor cells by blocking the growth factor receptors. Effects of antibody therapy are attained indirectly either by direct cell toxicity, binding complement, or by using macrophages and monocytes to destroy the target cell. This is also called antibody-mediated cell toxicity. The monoclonal antibody can also be conjugated to radioisotope, toxin or cytotoxic agent, which then binds to the antigen and causes cell death.
Another important application of monoclonal antibody is in the treatment of viral diseases, which are usually considered as untreatable. It can be used to classify a single strain of pathogen and developmental biologists use these to target specific molecules in an organism. For example, proteins responsible for cell differentiation in respiratory system can be found out using monoclonal antibodies. Unequivocal classification of blood groups is another application of monoclonal antibodies. Immunological assays using monoclonal antibodies against the marker antigen of tumor allows accurate detection of tumor cell type, nature of tumors and early cases of metastasis. Monoclonal antibodies can also be used for accurate detection of specific chromosomes of a given species.
Even though the uses and applications of monoclonal antibodies drive a positive impression on it, there are certain limitations for the successful utilization of the above mentioned therapies. The highly heterogeneous distribution of malignant cells opens a possibility that only some of the cells express tumor antigens. Also, the density of antigens can vary, making certain cases where too low concentration of expressed antigen makes the action of monoclonal antibody less effective. In addition to that, if the delivery of monoclonal antibody is to be done via the blood, the non-optimal tumor blood flow makes it difficult for the therapy to reach the target site. The binding of passive monoclonal antibodies can be prevented due to high interstitial pressure within the tumor cells and sometimes the therapeutic antibody binds to the freely floating antigen which is released from the malignant cell, which makes the therapy ineffective. An immune response to mouse cell line derived antibody is another challenge faced during clinical applications because this not only decreases the effect, but also wipes out the chances of a re-treatment.
In spite of these obstacles, research activities and detailed studies are progressing to overcome the same and it is certain that monoclonal antibodies provide a convincing solution to many unanswered problems faced by medical science.
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