17 Jun 2008 to 20 Jun 2008
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Fusion Antibodies will be exhibiting at BIO 2008 in San Diego, US
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Monoclonal Antibodies
An antibody is an immunoglobulin molecule capable of strongly recognising a specific antigen. Antibodies are produced by the immune system (white blood cells called B cells) in response to the presence of a substance considered by the organism as foreign or non-self such as bacteria or viruses.
In 1904 Paul Ehrlich coined the now famous term ‘magic bullets’ in reference to a method for specifically targeting diseased tissue. In 1975 Kohler and Milstein discovered a method for generating highly specific antibodies for a determined antigen using a mouse host B cell. They invented immortal monoclonal antibody secreting hybridoma cell lines and the key to the “magic bullet” was found.
Monoclonal antibodies derived from the progeny of a single immune cell can be purified and used as therapy to treat many diseases including cancer. Since the approval of the first mouse antibody for therapeutic use in 1986 (Anti CD3 for use in transplant rejection) technology has moved on apace to overcome potential reduced efficacy issues. Antibody engineering has led to the approval of a further 20 therapeutic antibodies with many more currently undergoing clinical trials.
Why Humanise?
The early therapeutic antibodies which were developed were fully mouse antibodies. When injected into patients, they were efficacious but multiple doses were less well tolerated as they triggered immune response. The patient recognised the mouse antibody as a foreign protein and developed antibodies against the drug (Human Anti-Mouse Antibody or HAMA). This HAMA response reduced antibody effectiveness by shortened monoclonal antibody half life but could also induce toxicity depending on the quantity of antibody injected.
To address this issue, monoclonal antibodies were engineered in order to make them “more human”. Scientists developed chimeric antibodies, which were still 67 % human. They have proven to be effective drugs but multiple doses still triggered a response in a subset of patients. That is the reason why other scientist developed CDR-grafted antibody (Humanized Antibody) with only 5 to 10 % mouse sequence. Nowadays technologies exist that allow 100% human antibodies to be engineered. This reduces the chance of an immune response and in certain cases can actually improve the efficacy of a target antibody by affinity maturation.