Transgenic animals monoclonal antibodies

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-... 

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... 

Overexpression of the EGF receptor (or any of its ligands), can also induce cancer in both cell lines and transgenic animal models. Monoclonal antibodies capable of blocking receptor activity can promote tumour regression in mice suffering from various carcinomas. A direct correlation also exists between elevated EGF receptor numbers and a shorter patient survival span in the case of several forms of breast, oesophageal, bladder and squamous cell carcinomas. 

Antibodies are expressed by hybridoma cells formed by cell fusion of sensitized animal or human B lymphocytes with myeloma cells, or they are generated by EBV (Epstein-Barr virus) transformation of sensitized B lymphocytes. Other heterologous expression systems such as bacteria, yeast, insect cells, and mammalian cells have also been used for expression of antibodies and their fragments. However, because of renaturation problems, glycosylation, and expression levels, mammalian cells are mostly used for the expression of monoclonal antibodies. More recently, technologies have been extensively developed for the expression of antibodies in transgenic animals and transgenic plants. 

Due to discrimination from species to species, protein A resins can be used to separate monoclonal antibodies from transgenic milk. Autologous antibodies are not adsorbed if the animal is well chosen. For instance, monoclonal humanized IgG expressed in goat milk can be separated. 

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].)... 

These data demonstrate the involvement of chemokines and their receptors in inflammatory joint disease. Further information on the role of chemokines and chemokine receptors should come from the use of transgenic or knockout mice in animal models of arthritis. It is clear that blocking the interactions between chemokines and their receptors using antichemokine, antichemokine receptor monoclonal antibodies, or chemokine receptor antagonists may prove to be of therapeutic value in the control inflammatory diseases such as rheumatoid arthritis. 

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. 

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