Monoclonal antibody production Transgenic animals

A further advance in antibody technology is the development of transgenic mouse human strains. XenoMouse animals have been engineered in such a way that they now produce exclusively human antibodies rather than murine antibodies when immunized. The use of XenoMouse animals to produce MAbs avoids the need for any engineering of the antibody genes, since the products are already 100% human protein. XenoMouse animals are fully compatible with standard hybridoma technology and can be readily adopted by laboratories experienced in monoclonal antibody production [56]. 

Points to Consider in the Manufacture and Testing of Monoclonal Antibody Products for Human Use Points to Consider on Plasmid DNA Vaccines for Preventive Infectious Disease Indications Points to Consider in the Manufacture and Testing of Therapeutic Products for Human Use Derived from Transgenic Animals... 

Antibodies were first expressed in transgenic plants in 1989. Since then various antibody fragments and domains have been produced in plant hosts as well as full-length and multimeric antibodies. The most popular host species for this work has been the tobacco plant, Nicotiana, although com and soybeans have also been utilized. There is no apparent reason why other plants could not be used. The value of using plants for monoclonal antibody production include the absence of animal pathogens, the ease of genetic manipulation, the ability of post-translational modification, and the potential for scale-up to an economic production process. 

The most widely studied therapeutic proteins produced in plants include monoclonal antibodies for passive immunotherapy and antigens for use as oral vaccines [40]. Antibodies against dental caries, rheumatoid arthritis, cholera, E. coli diarrhea, malaria, certain cancers, Norwalk virus, HIV, rhinovirus, influenza, hepatitis B virus and herpes simplex virus have been produced in transgenic plants. However, the anti-Streptococcus mutans secretory antibody for the prevention of dental caries is the only plant-derived antibody currently in Phase II clinical trials [40]. Until recently, most antibodies were expressed in tobacco, potato, alfalfa, soybean, rice and wheat [9], It has been estimated that for every 170 tons of harvested tobacco, 100 tons represents harvested leaves. A single hectare could thus yield 50 kg of secretory IgA [3, 41]. Furthermore, it has been estimated that the cost of antibody production in plants is half that in transgenic animals and 20 times lower than in mammalian cell cul-... 

The main focus on modem biopharmaceuticals should be directed towards novel products which will be either monoclonal antibodies, recombinant proteins, cell and gene therapeutics, or viral products. Apart from product classes, new approaches to manufacture are also advancing, with transgenic animals and plants complementing existing cell culture-based expression (see Part IV, Chapters 5-11). (For a recent review, see Ref [8].)... 

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