Molecular farming of antibodies in plants

  • Richard M. Twyman
  • Stefan Schillberg
  • Rainer Fischer

Abstract

Antibodies are multi-subunit glycoproteins, produced by the vertebrate immune system. They recognize and bind to their target antigens with great affinity and specificity, which allows them to be used for many applications, including the diagnosis, prevention and treatment of human and animal disease (Anderson and Krummen 2003; Chad and Chamow 2001; Fischer and Emans 2000). It is estimated that approximately 1000 therapeutic recombinant antibodies are under development, up to one quarter of which may already be undergoing clinical trials. A large proportion of these antibodies recognize cancer antigens but others have been developed for the diagnosis and treatment of infectious diseases, acquired disorders and even transplant rejection (Gavilondo and Larrick 2000). As well as biomedical applications, antibodies can also be exploited to prevent diseases in plants (Schillberg et al. 2001), to detect and remove environmental contaminants, and for various industrial processes such as affinity purification and molecular targeting (Stoger et al. 2005b).

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References

  1. Andersen DC, Krummen L (2003) Recombinant protein expression for therapeutic applications. Curr Opin Biotechnol 3: 117–123Google Scholar
  2. Artsaenko O, Kettig B, Fiedler U, Conrad U, Düring K (1998) Potato tubers as a biofactory for recombinant antibodies. Mol Breeding 4: 313–319Google Scholar
  3. Bai Y, Glatz CE (2003) Bioprocess considerations for expanded-bed chromatography of crude canola extract: sample preparation and adsorbent reuse. Biotechnol Bioeng 81: 775–782PubMedGoogle Scholar
  4. Bakker H, Bardor M, Molthoff JW, Gomord V, Elbers I, Stevens LH, Jordi W, Lommen A, Faye L, Lerouge P, Bosch D (2001) Galactose-extended glycans of antibodies produced by transgenic plants. Proc Natl Acad Sci USA 98: 2899–2904PubMedGoogle Scholar
  5. Baneyx F, Mujacic M (2004) Recombinant protein folding and misfolding in Escherichia coli. Nature Biotechnol 22: 1399–1408Google Scholar
  6. Benvenuto E, Ordas RJ, Tavazza R, Ancora G, Biocca S, Cattaneo A, Galeffi P (1991) ‘Phytoantibodies’: a general vector for the expression of immunoglobulin domains in transgenic plants. Plant Mol Biol 17: 865–874PubMedGoogle Scholar
  7. Blixt O, Allin K, Pereira L, Datta A, Paulson JC (2002) Efficient chemoenzymatic synthesis of O-linked sialyl oligosaccharides. J Am Chem Soc 124: 5739–5746PubMedGoogle Scholar
  8. Borisjuk NV, Borisjuk LG, Logendra S, Petersen F, Gleba Y, Raskin I (1999) Production of recombinant proteins in plant root exudates. Nature Biotechnol 17: 466–469Google Scholar
  9. Bouquin T, Thomsen M, Nielsen LK, Green TH, Mundy J, Hanefeld Dziegiel M (2002) Human anti-rhesus D IgG1 antibody produced in transgenic plants. Transgenic Res 11: 115–122PubMedGoogle Scholar
  10. Bruyns AM, De Jaeger G, De Neve M, De Wilde C, Van Montagu M, Depicker A (1996) Bacterial and plant-produced scFv proteins have similar antigenbinding properties. FEBS Lett 386: 5–10PubMedGoogle Scholar
  11. Cabanes-Macheteau M, Fitchette-Laine AC, Loutelier-Bourhis C, Lange C, Vine N, Ma J, Lerouge P, Faye L (1999) N-Glycosylation of a mouse IgG expressed in transgenic tobacco plants. Glycobiology 9: 365–372PubMedGoogle Scholar
  12. Canizares MC, Nicholson L, Lomonossoff GP (2005) Use of viral vectors for vaccine production in plants. Immunol Cell Biol 83: 263–270PubMedGoogle Scholar
  13. Chadd HE, Chamow SM (2001) Therapeutic antibody expression technology. Curr Opin Biotrechnol 12: 188–194Google Scholar
  14. Chargelegue D, Drake PM, Obregon P, Prada A, Fairweather N, Ma JK (2005) Highly immunogenic and protective recombinant vaccine candidate expressed in transgenic plants. Infect Immun 73: 5915–5922PubMedGoogle Scholar
  15. Christensen AH, Quail PH (1996) Ubiquitin promoter-based vectors for high-level expression of selectable and/or screenable marker genes in monocotyledonous plants. Transgenic Res 5: 213–218PubMedGoogle Scholar
  16. Christou P, Stoger E, Twyman RM (2004) Monocot systems for molecular farming. In: Fischer R, Schillberg S (eds) Molecular Farming: Plant-made Pharmaceuticals and Technical Proteins. John Wiley & Sons Inc., NY, pp 55–67Google Scholar
  17. Chu L, Robinson DK (2001) Industrial choices for protein production by largescale cell culture. Curr Opin Biotechnol 12: 180–187PubMedGoogle Scholar
  18. Commandeur U, Twyman RM, Fischer R (2003) The biosafety of molecular farming in plants. AgBiotechNet 5: ABN 110Google Scholar
  19. Conrad U, Fiedler U (1998) Compartment-specific accumulation of recombinant immunoglobulins in plant cells: an essential tool for antibody production and immunomodulation of physiological functions and pathogen activity. Plant Mol Biol 38: 101–109PubMedGoogle Scholar
  20. CPMP (2002) Points to consider on quality aspects of medicinal products containing active substances produced by stable transgene expression in higher plants (CPMP/BWP/764/02), The European Agency for the Evaluation of Medicinal Products (EMEA)Google Scholar
  21. Cramer CL, Boothe JG, Oishi KK (1999) Transgenic plants for therapeutic proteins: linking upstream and downstream technologies. Curr Top Microbiol & Immunol 240: 95–118Google Scholar
  22. D’Aoust MA, Lerouge P, Busse U, Bilodeau P, Trepanier S, Gomord V, Faye L, Vezina LP (2004) Efficient and reliable production of pharmaceuticals in alfalfa. In: Molecular Farming: Plant-made Pharmaceuticals and Technical Proteins (Fischer R, Schillberg S (eds). John Wiley & Sons, NY, 1–12Google Scholar
  23. Daniell H, Chebolu S, Kumar S, Singleton M, Falconer R (2005a) Chloroplastderived vaccine antigens and other therapeutic proteins. Vaccine 23: 1779–1783Google Scholar
  24. Daniell H, Kumar S, Dufourmantel N (2005b) Breakthrough in chloroplast genetic engineering of agronomically important crops. Trends Biotechnol 23: 238–245Google Scholar
  25. De Jaeger G, Scheffer S, Jacobs A, Zambre M, Zobell O, Goossens A, Depicker A, Angenon G (2002) Boosting heterologous protein production in transgenic dicotyledonous seeds using Phaseolus vulgaris regulatory sequences. Nature Biotechnol 20: 1265–1268Google Scholar
  26. De Neve M, De Loose M, Jacobs A, Van Houdt H, Kaluza B, Weidle U, Van Montagu M, Depicker A (1993) Assembly of an antibody and its derived antibody fragment in Nicotiana and Arabidopsis. Transgenic Res 2: 227–237PubMedGoogle Scholar
  27. De Wilde C, De Rycke R, Beeckman T, De Neve M, Van Montagu M, Engler G, Depicker A (1998) Accumulation pattern of IgG antibodies and Fab fragments in transgenic Arabidopsis thaliana plants. Plant Cell Physiol 39: 639–646PubMedGoogle Scholar
  28. De Wilde C, Peeters K, Jacobs A, Peck I, Depicker A (2002) Expression of antibodies and Fab fragments in transgenic potato plants: a case study for bulk production in crop plants. Mol Breeding 9: 271–282Google Scholar
  29. Decker EL, Reski R (2004) The moss bioreactor. Curr Opin Plant Biol 7: 166–170PubMedGoogle Scholar
  30. Donson J, Kearney CM, Hilf ME, Dawson WO (1991) Systemic expression of a bacterial gene by a tobacco mosaic virus-based vector. Proc Natl Acad Sci USA 88: 7204–7208PubMedGoogle Scholar
  31. Doran PM (2006) Loss of recombinant proteins from plant cell cultures. Trends Biotechnol (in press)Google Scholar
  32. Drake PM, Chargelegue DM, Vine ND, van Dolleweerd CJ, Obregon P, Ma JK (2003) Rhizosecretion of a monoclonal antibody protein complex from transgenic tobacco roots. Plant Mol Biol 52: 233–241PubMedGoogle Scholar
  33. Drossard J (2003) Downstream processing of plant-derived recombinant therapeutic proteins. In: Fischer R, Schillberg S (eds) Molecular Farming: Plant-made Pharmaceuticals and Technical Proteins. John Wiley & Sons Inc., NY, pp 217–231Google Scholar
  34. Dyck MK, Lacroix D, Pothier F, Sirard MA (2003) Making recombinant proteins in animals – different systems, different applications. Trends Biotechnol 21: 394–399PubMedGoogle Scholar
  35. Ehsani P, Meunier A, Nato F, Jafari A, Nato A, Lafaye P (2003) Expression of anti human IL-4 and IL-6 scFvs in transgenic tobacco plants. Plant Mol Biol 52: 17–29PubMedGoogle Scholar
  36. Fahrner RL, Knudsen HL, Basey CD, Galan W, Feuerhelm D, Vanderlaan M, Blank GS (2001) Industrial purification of pharmaceutical antibodies: development, operation, and validation of chromatography processes. Biotechnol Genet Eng Rev 18: 301–327PubMedGoogle Scholar
  37. Faye L, Boulaflous A, Benchabane M, Gomord V, Michaud D (2005) Protein modifications in the plant secretory pathway: current status and practical implications in molecular pharming. Vaccine 23: 1770–1778PubMedGoogle Scholar
  38. FDA (2002) Guidance for industry. Drugs, biologics, and medical devices derived from bioengineered plants for use in humans and animals. Food and Drug AdministrationGoogle Scholar
  39. Fischer R, Emans N, Schuster F, Hellwig S, Drossard J (1999) Towards molecular farming in the future: using plant-cell-suspension cultures as bioreactors. Biotechnol Appl Biochem 30: 109–112PubMedGoogle Scholar
  40. Fischer R, Emans N (2000) Molecular farming of pharmaceutical proteins. Transgenic Res 9: 279–299PubMedGoogle Scholar
  41. Francisco JA, Gawlak SL, Miller M, Bathe J, Russell D, Chace D, Mixan B, Zhao L, Fell HP, Siegall CB (1997) Expression and characterization of bryodin 1 and a bryodin 1-based single-chain immunotoxin from tobacco cell culture. Bioconjug Chem 8: 708–713PubMedGoogle Scholar
  42. Franconi R, Roggero P, Pirazzi P, Arias FJ, Desiderio A, Bitti O, Pashkoulov D, Mattei B, Bracci L, Masenga V, Milne RG, Benvenuto E (1999) Functional expression in bacteria and plants of an scFv antibody fragment against tospoviruses. Immunotechnology 4: 189–201PubMedGoogle Scholar
  43. Franklin SE, Mayfield SP (2005) Recent developments in the production of human therapeutic proteins in eukaryotic algae. Expert Opin Biol Ther 5: 225–235PubMedGoogle Scholar
  44. Gasdaska JR, Spencer D, Dickey L (2003) Advantages of therapeutic protein production in the aquatic plant Lemna. BioProcessing J Mar/Apr: 49–56Google Scholar
  45. Gavilondo JV, Larrick JW (2000) Antibody production technology in the millennium. Biotechniques 29: 128–145PubMedGoogle Scholar
  46. Gerngross TU (2004) Advances in the production of human therapeutic proteins in yeasts and filamentous fungi. Nature Biotechnol 22: 1409–1414Google Scholar
  47. Gleba Y, Marillonnet S, Klimyuk V (2004) Engineering viral expression vectors for plants: the ‘full virus’ and the ‘deconstructed virus’ strategies. Curr Opin Plant Biol 7: 182–188PubMedGoogle Scholar
  48. Gleba Y, Klimyuk V, Marillonnet S (2005) Magnifection – a new platform for expressing recombinant vaccines in plants. Vaccine 23: 2042–2048PubMedGoogle Scholar
  49. Gomord V, Sourrouille C, Fitchette AC, Bardor M, Pagny S, Lerouge P, Faye L (2004) Production and glycosylation of plant-made pharmaceuticals: the antibodies as a challenge. Plant Biotechnol J 2: 83–100PubMedGoogle Scholar
  50. Gomord V, Chamberlain P, Jefferis R, Faye L (2005) Biopharmaceutical production in plants: problems, solutions and opportunities. Trends Biotechnol 23: 559–565PubMedGoogle Scholar
  51. Green L (1999) Antibody engineering via genetic engineering of the mouse: xenomouse strains are a vehicle for the facile generation of therapeutic human monoclonal antibodies. J Immunol Methods 231: 11–23PubMedGoogle Scholar
  52. Griffiths A, Duncan A (1998) Strategies for selection of antibodies by phage display. Curr Opin Biotechnol 9: 102–108PubMedGoogle Scholar
  53. Harvey AJ, Speksnijder G, Baugh LR, Morris JA, Ivarie R (2002) Expression of exogenous protein in the egg white of transgenic chickens. Nature Biotechnol 20: 396–399Google Scholar
  54. Hellwig S, Drossard J, Twyman RM, Fischer R (2004) Plant cell cultures for the production of recombinant proteins. Nature Biotechnol 22: 1415–1422Google Scholar
  55. Hendy S, Chen ZC, Barker H, Santa Cruz S, Chapman S, Torrance L, Cockburn W, Whitelam GC (1999) Rapid production of single-chain Fv fragments in plants using a potato virus X episomal vector. J Immunol Methods 231: 137–146PubMedGoogle Scholar
  56. Hiatt A, Cafferkey R, Bowdish K (1989) Production of antibodies in transgenic plants. Nature 342: 76–78PubMedGoogle Scholar
  57. Hood EE, Woodard SL, Horn ME (2002) Monoclonal antibody manufacturing in transgenic plants – myths and realities. Curr Opin Biotechnol 13: 630–635PubMedGoogle Scholar
  58. Hull AK, Criscuolo CJ, Mett V, Groen H, Steeman W, Westra H, Chapman G, Legutki B, Baillie L, Yusibov V (2005) Human-derived, plant-produced monoclonal antibody for the treatment of anthrax. Vaccine 23: 2082–2086PubMedGoogle Scholar
  59. Ikonomou L, Schneider YJ, Agathos SN (2003) Insect cell culture for industrial production of recombinant proteins. Appl Microbiol Biotechnol 62: 1–20PubMedGoogle Scholar
  60. Jefferis R (2001) Glycosylation of human IgG antibodies: relevance to therapeutic applications. Biopharm 2001: 19–27Google Scholar
  61. Kapila J, De Rycke R, van Montagu M, Angenon G (1997) An Agrobacterium -mediated transient gene expression system for intact leaves. Plant Sci 122: 101–108Google Scholar
  62. Kathuria S, Sriraman R, Nath R, Sack M, Pal R, Artsaenko O, Talwar GP, Fischer R, Finnern R (2002) Efficacy of plant-produced recombinant antibodies against HCG. Hum Reprod 17: 2054–2061PubMedGoogle Scholar
  63. Khoudi H, Laberge S, Ferullo JM, Bazin R, Darveau A, Castonguay Y, Allard G, Lemieux R, Vezina LP (1999) Production of a diagnostic monoclonal antibody in perennial alfalfa plants. Biotechnol Bioeng 64: 135–143PubMedGoogle Scholar
  64. Kipriyanov SM, Little M (1999) Generation of recombinant antibodies. Mol Biotechnol 12: 173–201PubMedGoogle Scholar
  65. Ko K, Tekoah Y, Rudd PM, Harvey DJ, Dwek RA, Spitsin S, Hanlon CA, Rupprecht C, Dietzschold B, Golovkin M, Koprowski H (2003) Function and glycosylation of plant-derived antiviral monoclonal antibody. Proc Natl Acad Sci USA 100: 8013–8018PubMedGoogle Scholar
  66. Ko K, Steplewski Z, Glogowska M, Koprowski H (2005) Inhibition of tumor growth by plant-derived mAb. Proc Natl Acad Sci USA 102: 7026–7030PubMedGoogle Scholar
  67. Komarnytsky S, Borisjuk NV, Borisjuk LG, Alam MZ, Raskin I (2000) Production of recombinant proteins in tobacco guttation fluid. Plant Physiol 124: 927–933PubMedGoogle Scholar
  68. Lelivelt CL, McCabe MS, Newell CA, Desnoo CB, van Dun KM, Birch-Machin I, Gray JC, Mills KH, Nugent JM (2005) Stable plastid transformation in lettuce (Lactuca sativa L.) Plant Mol Biol 58: 763–774PubMedGoogle Scholar
  69. Ma JK, Hiatt A, Hein M, Vine ND, Wang F, Stabila P, van Dolleweerd C, Mostov K, Lehner T (1995) Generation and assembly of secretory antibodies in plants. Science 268: 716–719PubMedGoogle Scholar
  70. Ma JK, Drake PM, Christou P (2003) The production of recombinant pharmaceutical proteins in plants. Nat Rev Genet 4: 794–805PubMedGoogle Scholar
  71. Magee AM, Coyne S, Murphy D, Horvath EM, Medgyesy P, Kavanagh TA (2004) T7 RNA polymerase-directed expression of an antibody fragment transgene in plastids causes a semi-lethal pale-green seedling phenotype. Transgenic Res 13: 325–337PubMedGoogle Scholar
  72. Makvandi-Nejad S, McLean MD, Hirama T, Almquist KC, Mackenzie CR, Hall JC (2005) Transgenic tobacco plants expressing a dimeric single-chain variable fragment (scfv) antibody against Salmonella enterica serotype Paratyphi B. Transgenic Res 14: 785–792PubMedGoogle Scholar
  73. Maliga P (2003) Progress towards commercialization of plastid transformation technology. Trends Biotechnol 21: 20–28PubMedGoogle Scholar
  74. Maliga P (2004) Plastid transformation in higher plants. Annu Rev Plant Biol 55: 289–313PubMedGoogle Scholar
  75. Marillonnet S, Thoeringer C, Kandzia R, Klimyuk V, Gleba Y (2005) Systemic Agrobacterium tumefaciens-mediated transfection of viral replicons for efficient transient expression in plants. Nature Biotechnol 23: 718–723Google Scholar
  76. Mayfield SP, Franklin SE, Lerner RA (2003) Expression and assembly of a fully active antibody in algae. Proc Natl Acad Sci USA 100: 438–442PubMedGoogle Scholar
  77. Mayfield SP, Franklin SE (2005) Expression of human antibodies in eukaryotic micro-algae. Vaccine 23: 1828–1832PubMedGoogle Scholar
  78. McCormick AA, Kumagai MH, Hanley K, Turpen TH, Hakim I, Grill LK, Tuse D, Levy S, Levy R (1999) Rapid production of specific vaccines for lymphoma by expression of the tumor-derived single-chain Fv epitopes in tobacco plants. Proc Natl Acad Sci USA 96: 703–708PubMedGoogle Scholar
  79. Menkhaus TJ, Bai Y, Zhang C, Nikolov ZL, Glatz CE (2004) Considerations for the recovery of recombinant proteins from plants. Biotechnol Prog. 20: 1001–1014PubMedGoogle Scholar
  80. Menkhaus TJ, Glatz CE (2005) Antibody capture from corn endosperm extracts by packed bed and expanded bed adsorption. Biotechnol Prog. 21: 473–485PubMedGoogle Scholar
  81. Nikolov ZL, Woodard SL (2004) Downstream processing of recombinant proteins from transgenic feedstock. Curr Opin Biotechnol 15: 479–486PubMedGoogle Scholar
  82. Nugent GD, Coyne S, Nguyen TT, Kavanagh TA, Dix PJ (2006) Nuclear and plastid transformation of Brassica oleracea var. botrytis (cauliflower) using PEG-mediated uptake of DNA into protoplasts. Plant Sci 170: 135–142Google Scholar
  83. Padidam M (2003) Chemically regulated gene expression in plants. Curr Opin Plant Biol 6: 169–177PubMedGoogle Scholar
  84. Perrin Y, Vaquero C, Gerrard I, Sack M, Drossard J, Stoger E, Christou P, Fischer R (2000) Transgenic pea seeds as bioreactors for the production of a singlechain Fv fragment (scFV) antibody used in cancer diagnosis and therapy. Mol Breeding 6: 345–352Google Scholar
  85. Raju TS, Briggs J, Borge SM, Jones AJS (2000) Species-specific variation in glycosylation of IgG: evidence for the species-specific sialylation and branchspecific galactosylation and importance for engineering recombinant glycoprotein therapeutics. Glycobiolgy 10: 477–486Google Scholar
  86. Rodriguez M, Ramirez NI, Ayala M, Freyre F, Perez L, Triguero A, Mateo C, Selman-Housein G, Gavilondo JV, Pujol M (2005) Transient expression in tobacco leaves of an aglycosylated recombinant antibody against the epidermal growth factor receptor. Biotechnol Bioeng 89: 188–194PubMedGoogle Scholar
  87. Schaefer DG (2002) A new moss genetics: targeted mutagenesis in Physcomitrella patens. Annu Rev Plant Biol 53: 477–501PubMedGoogle Scholar
  88. Schillberg S, Zimmermann S, Voss A, Fischer R (1999) Apoplastic and cytosolic expression of full-size antibodies and antibody fragments in Nicotiana tabacum. Transgenic Res 8: 255–263PubMedGoogle Scholar
  89. Schillberg S, Zimmermann S, Zhang MY, Fischer R (2001) Antibody-based resistance to plant pathogens. Transgenic Res 10: 1–12PubMedGoogle Scholar
  90. Schillberg S, Emans N, Fischer R (2002) Antibody molecular farming in plants and plant cells. Phytochem Rev 1: 45–54Google Scholar
  91. Schillberg S, Fischer R, Emans N (2003) Molecular farming of recombinant antibodies in plants. Cell Mol Life Sci 60: 433–445PubMedGoogle Scholar
  92. Schunmann PHD, Coia G, Waterhouse PM (2002) Biopharming the SimpliREDTM HIV diagnostic reagent in barley, potato and tobacco. Mol. Breeding 9: 113–121Google Scholar
  93. Schunmann PHD, Surin B, Waterhouse PM (2003) A suite of novel promoters and terminators for plant biotechnology. II. The pPLEX series for use in monocots Funct Plant Biol 30: 453–460Google Scholar
  94. Semenyuk EG, Orlova IV, Stremovskii OA, Balandin TG, Nosov AM, Bur’yanov Y, Deev SM (2002) Transgenic tobacco plants produce miniantibodies against human ferritin. Dokl Biochem Biophys 384: 176–178PubMedGoogle Scholar
  95. Seveno M, Bardor M, Paccalet T, Gomord V, Lerouge P, Faye L (2004) Glycoprotein sialylation in plants? Nature Biotechnol 22: 1351–1352Google Scholar
  96. Shah MM, Fujiyama K, Flynn CR, Joshi L (2003) Sialylated endogenous glycoconjugates in plant cells. Nature Biotechnol 21: 1470–1471Google Scholar
  97. Shah MM, Fujiyama K, Flynn CR, Joshi L (2004) Glycoprotein sialylation in plants? Reply. Nature Biotechnol 22: 1352–1353Google Scholar
  98. Sharp JM, Doran PM (2001a) Characterization of monoclonal antibody fragments produced by plant cells. Biotechnol Bioeng 73: 338–346Google Scholar
  99. Sharp JM, Doran PM (2001b) Strategies for enhancing monoclonal antibody accumulation in plant cell and organ cultures. Biotechnol Prog 17: 979–992Google Scholar
  100. Sidhu SS (2000) Phage display in pharmaceutical biotechnology. Curr Opin Biotechnol 11: 610–616PubMedGoogle Scholar
  101. Sriraman R, Sack M, Talwar GP, Fischer R (2003) Glycosylation of recombinant antibodies in plants. In: Proceedings of the Ninth Annual Ranbaxy Science Foundation Symposium. Ranbaxy Science Foundation, New Delhi, pp 89–98Google Scholar
  102. Sriraman R, Bardor M, Sack M, Vaquero C, Faye L, Fischer R, Finnern R, Lerouge P (2004) Recombinant anti-hCG antibodies retained in the endoplasmic reticulum of transformed plants lack core-xylose and core- (1, 3)- fucose residues. Plant Biotechnol J 2: 279–287PubMedGoogle Scholar
  103. Stoger E, Vaquero C, Torres E, Sack M, Nicholson L, Drossard J, Williams S, Keen D, Perrin Y, Christou P, Fischer R (2000) Cereal crops as viable production and storage systems for pharmaceutical scFv antibodies. Plant Mol Biol 42: 583–590PubMedGoogle Scholar
  104. Stoger E, Sack M, Perrin Y, Vaquero C, Torres E, Twyman RM, Christou P, Fischer R (2002) Practical considerations for pharmaceutical antibody production in different crop systems. Mol Breeding 9: 149–158Google Scholar
  105. Stoger E, Ma JK, Fischer R, Christou P (2005a) Sowing the seeds of success: pharmaceutical proteins from plants. Curr Opin Biotechnol 16: 167–173Google Scholar
  106. Stoger E, Sack M, Nicholson L, Fischer R, Christou P (2005b) Recent progress in plantibody technology. Curr Pharm Des 11: 2439–2457Google Scholar
  107. Strasser R, Altmann F, Mach L, Glossl J, Steinkellner H (2004) Generation of Arabidopsis thaliana plants with complex N-glycans lacking beta1, 2-linked xylose and core alpha1, 3-linked fucose. FEBS Lett 561: 132–136PubMedGoogle Scholar
  108. Subroto MA, Hamill JD, Doran PM (1996) Development of shooty teratomas from several solanaceous plants: growth kinetics, stoichiometry and alkaloid production. J Biotechnol 45: 45–57Google Scholar
  109. Torres E, Vaquero C, Nicholson L, Sack M, Stoger E, Drossard J, Christou P, Fischer R, Perrin Y (1999) Rice cell culture as an alternative production system for functional diagnostic and therapeutic antibodies. Transgenic Res 8: 441–449PubMedGoogle Scholar
  110. Triguero A, Cabrera G, Cremata JA, Yuen CT, Wheeler J, Ramírez NI (2005) Plant-derived mouse IgG monoclonal antibody fused to KDEL endoplasmic reticulum-retention signal is N-glycosylated homogeneously throughout the plant with mostly high-mannose-type N-glycans. Plant Biotechnol J 3: 449–457PubMedGoogle Scholar
  111. Twyman RM, Stoger E, Schillberg S, Christou P, Fischer R (2003) Molecular farming in plants: host systems and expression technology. Trends Biotechnol 21: 570–578PubMedGoogle Scholar
  112. Twyman RM, Schillberg S, Fischer R (2005) Transgenic plants in the biopharmaceutical market. Expert Opin Emerg Drugs 10: 185–218PubMedGoogle Scholar
  113. Valdes R, Gomez L, Padilla S, Brito J, Reyes B, Alvarez T, Mendoza O, Herrera O, Ferro W, Pujol M, Leal V, Linares M, Hevia Y, Garcia C, Mila L, Garcia O, Sanchez R, Acosta A, Geada D, Paez R, Luis Vega J, Borroto C (2003a) Large-scale purification of an antibody directed against hepatitis B surface antigen from transgenic tobacco plants. Biochem Biophys Res Commun 308: 94–100Google Scholar
  114. Valdes R, Reyes B, Alvarez T, Garcia J, Montero JA, Figueroa A, Gomez L, Padilla S, Geada D, Abrahantes MC, Dorta L, Fernandez D, Mendoza O, Ramirez N, Rodriguez M, Pujol M, Borroto C, Brito J (2003b) Hepatitis B surface antigen immunopurification using a plant-derived specific antibody produced in large scale. Biochem Biophys Res Commun 310: 742–747Google Scholar
  115. Vaquero C, Sack M, Chandler J, Drossard J, Schuster F, Monecke M, Schillberg S, Fischer R (1999) Transient expression of a tumor-specific single-chain fragment and a chimeric antibody in tobacco leaves. Proc Natl Acad Sci USA 96: 11128–11133PubMedGoogle Scholar
  116. Vaquero C, Sack M, Schuster F, Finnern R, Drossard J, Schumann D, Reimann A, Fischer R (2002) A carcinoembryonic antigen-specific diabody produced in tobacco. FASEB J 16: 408–410PubMedGoogle Scholar
  117. Verch T, Yusibov V, Koprowski H (1998) Expression and assembly of a fulllength monoclonal antibody in plants using a plant virus vector. J Immunol Methods 220: 69–75PubMedGoogle Scholar
  118. Vine ND, Drake P, Hiatt A, Ma JK (2001) Assembly and plasma membrane targeting of recombinant immunoglobulin chains in plants with a murine immunoglobulin transmembrane sequence. Plant Mol Biol 45: 159–167PubMedGoogle Scholar
  119. Warner TG (2000) Metabolic engineering glycosylation: biotechnology’s challenge to the glycobiologist in the new millennium. In: Carbohydrates in Chemistry and Biology (Ernst B, Hart GW, Sanay P (eds), Wiley-VCH, NY, pp 1043–1064Google Scholar
  120. Wurm FM (2004) Production of recombinant protein therapeutics in cultivated mammalian cells. Nature Biotechnol 22: 1393–1398Google Scholar
  121. Yano A, Maeda F, Takekoshi M (2004) Transgenic tobacco cells producing the human monoclonal antibody to hepatitis B virus surface antigen. J Med Virol 73: 208–215PubMedGoogle Scholar
  122. Yusibov V, Rabindran S, Commandeur U, Twyman RM, Fischer R (2006) The potential of plant virus vectors for vaccine production. Drugs in R & D (in press)Google Scholar
  123. Zeitlin L, Olmsted SS, Moench TR, Co MS, Martinell BJ, Paradkar VM, Russell DR, Queen C, Cone RA, Whaley KJ (1998) A humanized monoclonal antibody produced in transgenic plants for immunoprotection of the vagina against genital herpes. Nature Biotechnol 16: 1361–1364Google Scholar
  124. Ziegler A, Cowan GH, Torrance L, Ross HA, Davies HV (2000) Facile assessment of cDNA constructs for expression of functional antibodies in plants using the potato virus X vector. Mol Breeding 6: 327–335Google Scholar
  125. Zimmermann S, Schillberg S, Liao YC, Fisher R (1998) Intracellular expression of TMV-specific single-chain Fv fragments leads to improved virus resistance in Nicotiana tabacum. Mol Breeding 4: 369–379Google Scholar

Copyright information

© Springer 2007

Authors and Affiliations

  • Richard M. Twyman
    • 1
  • Stefan Schillberg
    • 2
  • Rainer Fischer
    • 2
  1. 1.Department of BiologyUniversity of YorkYorkUnited Kingdom
  2. 2.Fraunhofer Institute for Molecular Biology and Applied Ecology (IME)AachenGermany

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