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What Are Mouse Antibodies?

By Ray Hawk
Updated Jan 22, 2024
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Mouse antibodies, often also referred to as monoclonal antibodies, are immunoglobulin molecules that are capable of binding to a specific site on an antigen, which can stimulate the natural production of antibodies in human immune systems. Antibodies are used by the immune system to recognize the presence of foreign material, such as viruses and bacteria, and target it for destruction. Production of monoclonal mouse antibodies first began in 1975, when researchers Niels K. Jerne, Georges J.F. Kohler, and Cesar Milstein discovered a method to generate specific antibodies from a mouse tissue known as the mouse host B cell. The researchers were able to produce cell lines still used today as a form of therapy to treat many diseases including cancer, and, for this, they won the Nobel Prize in Physiology or Medicine in 1984. By 1987, hybridoma cells, a merging of a cancer cell with a normal cell in the laboratory, were being used to rapidly produce mouse antibodies, known as Mabs, for medical diagnostics.

Antibody production using mouse antibodies was a breakthrough for medical research and treatment of diseases. These antibodies proved to be more abundant and uniform than a person's natural antibodies, and were, therefore, seen as a useful way to boost the ability of immune systems to fight off disease. Research antibodies are now produced for a variety of uses including measuring drug levels in serum, identifying infectious agents, typing blood and tissue, for classifying various forms of leukemia and lymphomas, and more. Custom antibodies also began to be produced in close relatives of mice, including hamsters and rats, as well as other species such as goats and sheep.

As therapeutic use of mouse antibodies became widespread, problems began to surface. Initial treatments in patients were well-tolerated, but, as subsequent treatments continued, the human body began to demonstrate a immune response to mouse proteins by generating human antibodies against them. This response is known as the human anti-mouse antibodies response (HAMA) and it can completely neutralize the beneficial effect of treatment with mouse antibodies, as well as cause allergic responses in some patients. In order to minimize adverse events, recombinant DNA processes were used to replace up to 70% of the mouse antibody protein with a human protein sequence. This refinement process was led by Greg Winter in 1986 at Cambridge University in the UK, and reduced the total quantity of original mouse tissue in the antibody to 5-10%, which made it much better tolerated as a therapy.

Recent technology now allows for the genetic engineering of 100% human antibodies for research and therapeutic treatments. As well, the most effective method of generating large amounts of mouse antibodies in the lab, the Freund Complete Adjuvant (FCA) process, created painful inflammatory lesions in the mice, and became a heated target of protest by animal rights groups such as the US based American Anti-Vivisection Society. This subsequently led to US federal organizations such as the National Institutes of Health (NIH), and European nations such as Switzerland and Germany requiring that in vitro production of mouse antibodies be used over the use of adult lab animals.

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