(May 31, 2004)
Research breakthrough in bovine production of human antibodies
World's first development of novel method to produce cows with disrupted
endogenous antibody and BSE-causative Prion genes.
Kirin Brewery Company, Limited (Kirin), as part of its joint project with Hematech LLC (Hematech) to develop a cow that can produce human antibodies, has succeeded in producing a cow embryo in which neither bovine antibody gene1 nor the gene for the prions2 that are the cause of BSE are present. The process developed by Kirin and Hematech utilizes cells derived from bovine embryos that continuously destroy the bovine genes for antibodies and prions.
This is the first successful production of a cell that continuously destroys two differing genes, and the first time that a cow embryo with these characteristics has been created through cell nuclear transfer.
A human antibody-producing cow is one that has had human antibody introduced to it, and R&D based on this facility is expected to make possible the development of a range of human antibody drugs. In 2002 Kirin made use of a proprietary human artificial chromosome vector to introduce a human antibody gene into bovine cells, and using Hematech technology created a cow capable of producing human antibody proteins and bovine antibody proteins. Subsequently, Kirin and Hematech have progressed to developing cows that can efficiently produce human antibodies-without producing their own antibodies-and cows that in theory cannot contract BSE.
As a result, the companies developed a cow embryo that produces neither bovine antibody genes nor prion genes. This was achieved by using cells derived from bovine embryos to produce cells that continuously destroy bovine antibody genes and the prion genes that cause BSE.
The latest research breakthrough dramatically reduces the time necessary to create a human antibody-producing cow, and simplifies the refining process required to separate human antibodies and bovine antibodies. It is expected to significantly speed up the research and commercialization of human antibody-producing cows and of polyclonal3 antibody pharmaceuticals.
Kirin has already successfully developed a human antibody-producing mouse, and has formed a strategic alliance with US company Medarex, Inc. to commercialize this technology on a global basis.
Whereas human antibody-producing mice are used for the development of monoclonal antibodies, human antibody-producing cows will be used for the development of polyclonal antibodies, which are expected to contribute to the development of treatments for viral or bacterial infections, autoimmune disorders, and other medical conditions.
The pharmaceutical industry currently uses gamma globulin preparations extracted and refined from human blood serum. By making use of human antibody-producing cows it will become possible to create an efficient, safe, and steady supply of polyclonal antibodies. This is expected to have widespread implications for the development of new medicines to combat a variety of infective and other conditions.
Kirin is continuing to undertake R&D in this field, with the aim of developing human antibody drugs and human antibody-related technologies.
1 By destroying bovine antibody genes the efficient production of human antibodies becomes possible.
2 Prion = Proteinaceous Infectious Particle. Normal prions also exist in ordinary cows; when these become abnormal they can become a causative factor in BSE.
3 Polyclonal antibodies are composite antibodies that react to multiple antigens. Monoclonal antibodies respond to only one type of antigen.