The therapeutic gap between antibodies from mice and humans has been eliminated in genetic engineering by GenPharm International.
The Mountain View, Calif., company reported in the June issue of Nature Genetics that its scientists have transferred a complete segment of the human heavy chain antibody gene into mice that had previously had their own antibody genes knocked out. The embryonic mice grow up producing human antibody subunits that can be used to generate completely human monoclonal antibodies.
Jonathan MacQuitty, chief executive officer of the transgenic animal company, said this approach may eventually be found easier than "humanizing" mouse antibodies by replacing the constant region of the antibody chain. Mouse antibodies are not safe for repeated administration because a large number of patients become sensitized to the foreign substance and develop dangerous immune reactions on repeat exposure. In humanized mouse MAbs, MacQuitty said, the variable region still retains the potential of invoking an immune reaction, which could limit the utility of repeated treatments.
The developments reported in Nature Genetics detail the scientists' success at integrating large intact pieces of human DNA into the mouse germ line so the trait will be passed to offspring as mice colonies are established. Long DNA sequences shear easily and are difficult to manipulate.
The technology may be applied to developing therapeutics for such conditions as rheumatoid arthritis, transplant rejection, chronic inflammation and perhaps cancer, said GenPharm scientist Jeanne Loring. The work was based on techniques developed at the company and at the Massachusetts Institute of Technology, where the company's scientific adviser, Rudolf Jaenisch, works.
GenPharm received its first two U.S. patents underpinning this work earlier this year. At the end of 1992, the privately held company announced a research and license agreement with Eli Lilly and Co. concerning immunoconjugates for targeting toxins to tumors. Lilly obtained less than 5 percent equity in GenPharm and will pay benchmark and royalty fees.
-- Nancy Garcia Associate Editor
(c) 1997 American Health Consultants. All rights reserved.