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sensitivity and specificity are the main reasons why antibodies are so useful in research and in the clinic. Historically, antibodies have been manufactured by exploiting the immune response of various mammals (from rabbits to goats). Inoculation of these animals with an “antigen” (the molecule to be targeted) results in an immune response, and the production of antibodies which recognise this target. The serum of these animals contains multiple different antibodies which can recognise and bind the antigen, known as polyclonal antibodies. However these antibodies only make up a proportion of the total antibodies within the serum, the majority of which do not bind this antigen. The presence of these “non-specific” antibodies, in addition to batch-to-batch variation, can cause problems downstream. In research this can obscure results and cause problems with reproducibility. In the clinic this can cause toxicity problems and dosage uncertainties. Hence, although polyclonal antibodies have been used in the past for treatment of various diseases, it was the development of monoclonal antibody production in 1975 which revolutionised this field. Monoclonal antibody production is a technique involving the fusion of an antibody-producing B cell and an immortal cancer cell line to form a hybridoma. These hybridoma cell lines can be continuously cultured and expanded for the production of a single type of antibody of a desired specificity known as monoclonal antibodies. The first therapeutic monoclonal antibody OKT3 was used for the prevention of kidney transplant rejection. However, these non-human antibodies were picked up by the body as foreign and quickly cleared up by our immune system, becoming subsequently ineffective and even toxic. This technique has since been improved by engineering chimeric antibodies (70% human) and “humanized” antibodies (85-90% human). Although the majority of approved monoclonal antibod28

THE TRIPLE HELIX Spring 2016

ies have been created in this way, more recent technologies such as phage-display techniques, in addition to transgenic ‘humanized mice’, have allowed for the development of fully-human antibodies. For example Humira (adalimumab), the first fully-human therapeutic antibody, was developed using phage-display technology. Developed for the treatment of rheumatoid arthritis, Humira was licensed for therapy in 2003, and has since been used as medication for a variety of different auto-immune diseases, become the world’s best-selling prescription drug. These antibodies have been used in laboratories for decades, and are today used for a huge variety of laboratory techniques. You will probably have already come across fluorescent-microscope images, performed using fluorescently-tagged antibodies which are specific for certain cellular structures. Within the clinic, antibodies are useful for the diagnosis of a huge variety of diseases - many blood tests utilise antibodies for the detection of aberrant cells (such as cancers), infections (such as HIV), auto-antibodies (in autoimmune diseases), or the presence of specific biological indicators/markers (e.g. in pregnancy tests). Most importantly, antibodies can be also be used as drugs for the treatment of diseases. We are now seeing a boom in this industry, with 44 monoclonal antibodies and their derivatives already licensed for use in clinic (as of November 2014) [4], and hundreds more in the pre-clinical stages. In fact 6 out of 10 of the best selling drugs today are monoclonal antibodies, and account for over a third of new drugs being introduced [5]. These antibodies can be used to tag dangerous cells, such as cancerous or auto-immune cells, resulting in their neutralisation or destruction either directly via the immune response. Alternatively, binding of antibodies to specific sites on the receptors of cells can result in either blockage or activation of particular signalling pathways, altering the behaviour of cells. Antibodies can also © 2016, The Triple Helix, Inc. All rights reserved.

Science in Society Review - Spring 2016  
Science in Society Review - Spring 2016  
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