Monoclonal antibodies Transgenic

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-... 

Fig. 8.1 Western blot analysis of transgenic lines showing the expression of an assembled monoclonal antibody in transgenic chloroplasts. Lane 1 Extract from a chloroplast transgenic line, Lane 2 Extract from an untransformed plant. Lane 3 Positive control (human IgA). The gel was run under non-reducing conditions. The antibody was detected with an AP-conjugated goat anti-human kappa antibody.

Siegel, S.A. et al., The mouse/human chimeric monoclonal antibody cA2 neutralizes TNF in vitro and protects transgenic mice from cachexia and TNF lethality in vivo, Cytokine, 7, 26, 1995. 

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]. 

KeUermann S-A, Green LL. Antibody discovery the use of transgenic mice to generate human monoclonal antibodies for therapeutics. Curr Opin Biotechnol 2002 13 593-97. 

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. 

Drake, P.M., Chargelegue, D.M., Vine, N.D., van Dolleweerd, C.J., Obregon, P, and Ma, J.K. (2003). Rhizosecretion of a monoclonal antibody protein complex from transgenic tobacco roots. Plant Mol. Biol. 52 233-241. 

Hood, E.E., Woodard, S.L., and Hon, M.E. (2002). Monoclonal antibody manufacturing in transgenic plants myths and realities. Curr. Opin. Biotechnol. 13(6) 630-635. 

Yano, A., Maeda, E, and Takekoshi, M. (2004). Transgenic tobacco cells producing the human monoclonal antibody to hepatitis B virus surface antigen. J. Med. Virol 73 208-215. 

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