Antibody production by molecular farming in plants.
"Molecular farming" is the production of pharmaceutical proteins in transgenic plants and has great potential for the production of therapeutic anti-cancer antibodies and recombinant therapeutic proteins. Plants make fully functional recombinant human or animal antibodies. Cultivating transgenic plants on an agricultural scale will produce almost unlimited supplies of recombinant proteins for uses in medicine. Combinatorial library technology is a key tool for the generation and optimisation of therapeutic antibodies ahead of their expression in plants. Optimised antibody expression can be rapidly verified using transient expression assays in plants before creation of transgenic suspension cells or plant lines. Subcellular targeting signals that increase expression levels and optimise protein stability can be identified and exploited using transient expression to create high expresser plant lines. When high expresser lines have been selected, the final step is the development of efficient purification methods to retrieve functional antibody. Antibody production on an industrial scale is then possible using plant suspension cell culture in fermenters, or by the propagation of stably transformed plant lines in the field. Recombinant proteins can be produced either in whole plants or in seeds and tubers, which can be used for the long-term storage of both the protein and its production system. The review will discuss these developments and how we are moving toward the molecular farming of therapeutic antibodies becoming an economic and clinical reality.
Fischer
R
R
Institut für Biologie I, Botanik/Molekulargenetik, RWTH Aachen, Germany. fischer@biol.rwth-aachen.de
Hoffmann
K
K
Schillberg
S
S
Emans
N
N
D000818:Animals; D000906:Antibodies / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D019149:Bioreactors; D019496:Cancer Vaccines / Q000096:biosynthesis; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods; D002478:Cells, Cultured; D020650:Combinatorial Chemistry Techniques; D018506:Gene Expression Regulation, Plant; D005803:Genes, Immunoglobulin; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D018517:Plant Roots; D030821:Plants, Genetically Modified / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D012639:Seeds; D013535:Suspensions; D014027:Tobacco Mosaic Virus / Q000235:genetics
D000906:Antibodies; D019496:Cancer Vaccines; D011993:Recombinant Fusion Proteins; D013535:Suspensions