Transgenic plants 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-... 

Fig. 8.10 Titers of antibodies at day 50 induced by plant-derived CTB-2L21 recombinant protein. Balb/c mice were intraperitoneally immunized with leaf extract from CTB-2L21 transgenic plants. Animals were boosted at days 21 and 35. Each mouse received 20 pg of CTB-2L21 recombinant protein. Individual samples of mouse serum were titrated against 2L21 synthetic peptide,VP2 protein and a control peptide (amino acids 122-135 of hepatitis B virus surface antigen). Titers were expressed as the highest serum dilution to yield twice the absorbance mean of preimmune sera. M1-M6 mice 1 to 6 2L21 epitope from the VP2 protein of the canine parvovirus CTB cholera toxin B VP2 protein of the canine parvovirus that includes the 2L21 epitope.

The ability to stack genes in transgenic plants by successive crosses between individually transformed parental plants is a considerable advantage in attempting to construct multimeric protein complexes, such as secretory antibodies. As described earher, slgA consists of two basic Ig monomeric units (heavy and tight chains) that are dimerized by a joining (J) chain and then associated with a fourth polypeptide, the secretory component (SC) [36]. 

Tab. 15.1 Therapeutic antibodies produced in transgenic plants. See Fig. 15.1 for structures of the different antibodies and antibody fragments presented in the second column. Abbreviations TSP, total soluble protein FLW, fresh leafweight MSP, murine signal peptide SP, signal peptide KDEL, ER retention signal. In the column Expression + and - means respectively that the antibody was or was not expressed. 

Fig. 15.4 Structure of glycans N-linked to IgG molecules expressed in hybridomas and transgenic plants. Glycans N-linked to plant-derived antibodies are structurally different from their mammalian counterparts. In contrast with antibodies produced in alfalfa, antibodies produced in tobacco plants present a very high glycan heterogeneity.

USE OF RECOMBINANT scFv ANTIBODIES TO DISRUPT FLAVONOID METABOLISM IN TRANSGENIC PLANTS... 

Hiatt A, Caffferkey R, Bowdish K. (1989) Production of antibodies in transgenic plants. Nature 342 76-78. 

In 1990, the first plant-made vaccines were performed via expression of Streptococcus mutans surface protein A in transgenic tobacco, followed by oral immunization of mice with the same plant material (Fischer and Emans, 2000). This transgenic plant material was later shown to successfully induce an antibody response through a demonstration that serum from immunized mice could react with intact S. mutans. Plants were also developed that expressed Escherichia coli enterotoxin B subunit (LT-B) and that exhibited successful inducement of both mucosal and serum antibody responses (Tacket, 2005). These initial experiments led to a cornucopia of studies involving generations of plant-made vaccines and therapeutic proteins and their applications in medicine. 

A wide range of antibody formats have been expressed in transgenic plants and also shown to work effectively (Table 2.1). Plants are very efficient at producing immunoglobulins because of the great similarity in folding and... 

Galeffi, R, Lombardi, A., Donato, M.D., Latini, A., Sperandei, M., Cantale, C., and Giacomini, P. (2005). Expression of single-chain antibodies in transgenic plants. Vaccine 23(15) 1823-1827. 

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. 

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