Fully Human Antibody Production Technology
“Human antibodies” are those derived from human immune system. When antibodies produced by mice or rabbits are used in humans, they are effective against antigens in the first-dose, but from the second-dose onwards those xenogeneic antibodies are recognized by the human immune system as foreign antigens and hence eliminated immediately after dosing. Thus, it is known that such animal antibodies are not sufficiently effective in the long-term. Hence we forcused on the establishment of the Fully Human Antibody Production Technology, which produces antibodies equivalent to those of humans by animals, and eventually success was achieved with the creation of the KM Mouse that support antibody drug production.
HAC Technology
In previous gene transfer methods, the large size of human antibody genes limited them to partial injection only, meaning that it was impossible to transfer the same diversity of antibodies as existent in human bodies. However, Kyowa Hakko Kirin pioneered an epochal technique (Human Artificial Chromosome) of transferring a fragment of a human chromosome containing a very large cluster of genes into a mouse. By fusing this technique with the human antibody producing technology of the U.S. company Medarex Inc., the Human Antibody Producing Mouse (KM Mouse) was created, This technology is considered as the most advanced technology in this world.
By doing so we have been able to create antibody-producing mice that can generate fully human antibodies with the same diversity as in humans, opening the doors to continued investment leading to actual medical products utilizing this technology.
- * Reprint from Nature Biotechnology 20 and 889-894,2002
Monoclonal antibodies
Under normal circumstances, antibodies existing in the serum of animals immunized with antigens are a mix of various types of antibody molecules (polyclonal). Antigens often have multiple antigenic determinants (epitopes), hence polyclonal antibodies include molecules with mutually differing specificities. In contrast, monoclonal antibodies consist of single antibody reacting with a specific epitope.
By fusing mouse cells producing human antibodies against targeted antigens with myeloma cells to create autonomously replicating hybridoma, it is possible to select for only cells producing antibodies with the target specificity. Large volumes of human monoclonal antibodies can be produced by cultivation such cells and purification the antibodies secreted from them.
Monoclonal antibodies recognize specific antigens(epitopes) only and are thus able to effectively pinpoint and attack the foreign substances (disease-causing agents and cancer cells). Hence they have fewer side effects and are expected to be well suited to the treatment of cancer.
Polyclonal antibodies
Hematech, Inc.,U.S. subsidiary of Kyowa Hakko Kirin., has developed highly successful technology for the production of transgenic (genetically modified) cattle. Through the combination of Kyowa Hakko Kirin's Human Artificial Chromosomes (HAC) technologies, we have successfully achieved the creation of cattle producing human antibodies. Immunizing these cows with target antigens allows the production of human polyclonal antibodies, bringing us closer towards the practical application of these polyclonal antibodies. Polyclonal antibodies are considered to be effective in fighting infectious diseases with various antigens, and the human polyclonal antibodies have high hopes as ground-breaking pharmaceuticals to replace the previous immunoglobulin drug preparations made from animal-derived polyclonal antibodies.
