Molecular farming of recombinant antibodies in plants

Cellular and Molecular Life Sciences

Volumn 60, Issue 3, 2003, Pages 433-445

  Schillberg, S ^a   Fischer, R ^a,b   Emans, N ^b  

^a FRAUNHOFER INSTITUTE FOR MOLECULAR BIOLOGY AND APPLIED ECOLOGY IME   (Germany)

^b RWTH AACHEN UNIVERSITY   (Germany)

Author keywords

Antibody production; Biotechnology; Purification; Recombinant protein; Transgenic plant

Indexed keywords

CARCINOEMBRYONIC ANTIBODY; CELLGENESYS; GENZYME; IMMUNOGLOBULIN A; IMMUNOGLOBULIN F(AB) FRAGMENT; IMMUNOGLOBULIN G; IMMUNOGLOBULIN G1; LIGAND; MONOCLONAL ANTIBODY; MONOCLONAL ANTIBODY LEWIS Y; RECOMBINANT ANTIBODY; RECOMBINANT PROTEIN; SECRETORY IMMUNOGLOBULIN; SINGLE CHAIN FRAGMENT VARIABLE ANTIBODY; TUMOR ANTIGEN; UNCLASSIFIED DRUG; VIRUS ANTIBODY;

ANTIBODY PRODUCTION; BACTERIAL CELL; BIOTECHNOLOGY; CELL CULTURE; CELL LINE; CELLULAR DISTRIBUTION; CLINICAL TRIAL; COST EFFECTIVENESS ANALYSIS; CROP; DRUG COST; DRUG MANUFACTURE; DRUG QUALITY; EXPRESSION VECTOR; GENE TRANSFER; GENETIC TRANSCRIPTION; HERPES SIMPLEX VIRUS 2; HUMAN; MAMMAL; MOLECULAR CLONING; NONHUMAN; PLANT CELL; PROTEIN EXPRESSION; PROTEIN MODIFICATION; PROTEIN SYNTHESIS; PROTEIN TARGETING; REVIEW; SUSPENSION CELL CULTURE; TRANSGENE; TRANSGENIC ANIMAL; TRANSGENIC PLANT; YEAST CELL;

ANIMALS; ANTIBODIES; CLONING, MOLECULAR; PLANTS, GENETICALLY MODIFIED; RECOMBINANT PROTEINS;

ANIMALIA; BACTERIA (MICROORGANISMS); EMBRYOPHYTA; HERPES; HUMAN HERPESVIRUS 2; MAMMALIA;

EID: 0037362471     PISSN: 1420682X     EISSN: None     Source Type: Journal    
DOI: 10.1007/s000180300037     Document Type: Review

References (107)

1. Fischer R. and Emans N. (2000) Molecular farming of pharmaceutical proteins. Transgen. Res. 9: 279-299
2. Giddings G. (2001) Transgenic plants as protein factories. Curr. Opin. Biotechnol. 12: 450-454
3. Hood E. E. (2002) From green plants to industrial enzymes. Enzyme Microbiol. Technol. 30: 279-283
4. Andersen D. C. and Krummen L. (2002) Recombinant protein expression for therapeutic applications. Curr. Opin. Biotechnol. 13: 117-123
5. Chadd H. E. and Chamow S. M. (2001) Therapeutic antibody expression technology. Curr. Opin. Biotechnol. 12: 188-194
6. Jefferis R., Lund J. and Pound J. (1998) IgG-Fc mediated effector functions: molecular definition of interaction sites for effector ligands and the role of glycosylation. Immunol. Rev. 163: 50-76
7. Kipriyanov S. M. and Little M. (1999) Generation of recombinant antibodies. Mol. Biotechnol. 12: 173-201
8. Goeddel D. V., Heyneker H. L., Hozumi T., Arentzen R., Itakura K., Yansura D. G. et al. (1979) Direct expression in Escherichia coli of a DNA sequence coding for human growth hormone. Nature 281: 544-548
9. Goeddel D. V., Kleid D. G., Bolivar F., Heyneker H. L., Yansura D. G., Crea R. et al. (1979) Expression in Escherichia coli of chemically synthesized genes for human insulin. Proc. Natl. Acad. Sci. USA 76: 106-110
10. Martial J. A., Hallewell R. A., Baxter J. D. and Goodman H. M. (1979) Human growth hormone: complementary DNA cloning and expression in bacteria. Science 205: 602-607
11. Sánchez L., Ayala M., Freyre F., Pedroso I., Bell H., Falcón V. et al. (1999) High cytoplasmic expression in E. coli, purification and in vitro refolding of a single chain Fv antibody fragment against the hepatitis B surface antigen. J. Biotechnol. 72: 13-20
12. Cupit P. M., Whyte J. A., Porter A. J., Browne M. J., Holmes S. D., Harris W. J. et al. (1999) Cloning and expression of single chain antibody fragments in Escherichia coli and Pichia pastoris. Lett. Appl. Microbiol. 29: 273-277
13. Simmons L. C., Reilly D., Klimowski L., Raju T. S., Meng G., Sims P. et al. (2002) Expression of full-length immunoglobulins in Escherichia coli: rapid and efficient production of aglycosylated antibodies. J. Immunol. Methods 263: 133-147
14. Bretthauer R. K. and Castellino F. J. (1999) Glycosylation of Pichia pastoris-derived proteins. Biotechnol. Appl. Biochem. 30: 193-200
15. Freyre F., Vázquez J. E., Ayala M., Canaán-Haden L., Bell H., Rodríguez I. et al. (2000) Very high expression of an anti-carcinoembryonic antigen single chain Fv antibody fragment in the yeast Pichia pastoris. J. Biotechnol. 76: 157-163
16. Chu L. and Robinson D. K. (2001) Industrial choices for protein production by large-scale cell culture. Curr. Opin. Biotechnol. 12: 180-187
17. Yoo E. M., Chintalacharuvu K. R., Penichet M. L. and Morrison S. L. (2002) Myeloma expression systems. J. Immunol. Methods 261: 1-20
18. Reavy B., Ziegler A., Diplexcito J. and Macintosh S. M. (2000) Expression of functional recombinant antibody molecules in insect cell expression systems. Protein Express. Purif. 18: 221-228
19. Raju T. S., Briggs J., Borge S. M. and Jones A. J. S. (2000) Species-specific variation in glycosylation of IgG: evidence for the species-specific sialylation and branch-specific galactosylation and importance for engineering recombinant glycoprotein therapeutics. Glycobiolgy 10: 477-486
20. Umana P., Jean-Mairet J., Moudry R., Amstutz H. and Bailey J. E. (1999) Engineered glycoforms of an antineuroblastoma IgG1 with optimized antibody-dependent cellular cytotoxic activity. Nat. Biotechnol. 17: 176-180
21. Houdebaine L. M. (2000) Transgenic animal bioreactors. Transgen. Res. 9: 305-320
22. Castilla J., Pintado B., Sola I, Sanchez-Morgado J. and Enjuanes L. (1998) Engineering passive immunity in transgenic mice secreting virus-neutralizing antibodies in milk. Nat. Biotechnol. 16: 349-354
23. Wall R. (1999) Biotechnology for the production of modified and innovative animal products: transgenic livestock bioreactors. Livestock Prod. Sci. 59: 243-255
24. Pollock D., Kutzko J., Birck-Wilson E., Williams J., Echelard Y. and Meade H. (1999) Transgenic milk as a method for the production of recombinant antibodies. J. Immunol. Methods 231: 147-157
25. Tackett C. O. and Mason H. S. (1999) A review of oral vaccination with transgenic vegetables. Microbes Infect. 1: 777-783
26. Walmsely A. M. and Arntzen C. J. (2000) Plants for delivery of edible vaccines. Curr. Opin. Biotechnol. 11: 126-129
27. Vaquero C., Sack M., Chandler J., Drossard J., Schuster F., Monecke M. et al. (1999) Transient expression of a tumor-specific single chain fragment and a chimeric antibody in tobacco leaves. Proc. Natl. Acad. Sci. USA 96: 11128-11133
28. Ma J. K., Hiatt A., Hein M., Vine N. D., Wang F., Stabila P. et al. (1995) Generation and assembly of secretory antibodies in plants. Science 268: 716-719
29. Larrick J. W., Yu L., Naftzger C., Jaiswal S. and Wycoff K. (2001) Production of secretory IgA antibodies in plants. Biomol. Eng. 18: 87-94
30. Cabanes-Macheteau M., Fitchette-Laine A. C., Loutelier-Bourhis C., Lange C., Vine N., Ma J. et al. (1999) N-Glycosylation of a mouse IgG expressed in transgenic tobacco plants. Glycobiology 9: 365-372
31. Chargelegue D., Vine N., Dolleweerd C. van, Drake P. M. and Ma J. (2000) A murine monoclonal antibody produced in transgenic plants with plant-specific glycans is not immunogenic in mice. Transgen. Res. 9: 187-194
32. Bakker H., Bardor M., Molthoff J. W., Gomord V., Elbers I., Stevens L. H. et al. (2001) Galactose-extended glycans of antibodies produced by transgenic plants. Proc. Natl. Acad. Sci. USA 98: 2899-2904
33. De Neve M., De Loose M., Jacobs A., Van Houdt H., Kaluza B., Weidle U. et al. (1993) Assembly of an antibody and its derived antibody fragment in Nicotiana and Arabidopsis. Transgen. Res. 2: 227-237
34. De Wilde C., De Neve M., De Rycke R., Bruyns A. M., De Jaeger G., Van Montagu M. et al. (1996) Intact antigen-binding MAK33 antibody and Fab fragment accumulate in intercellular spaces of Arabidopsis thaliana. Plant Sci. 114: 233-241
35. Peeters K., De Wilde C. and Depicker A. (2001) Highly efficient targeting and accumulation of a Fab fragment within the secretory pathway and apoplast of Arabidopsis thaliana. Eur. J. Biochem. 268: 4251-4260
36. Artsaenko O., Peisker M., Nieden U. zur, Fiedler U., Weiler E. W., Müntz K. et al. (1995) Expression of a single-chain Fv antibody against abscisic acid creates a wilty phenotype in transgenic tobacco. Plant J. 8: 745-750
37. Owen M., Gandecha A., Cockburn B. and Whitelam G. (1992) Synthesis of a functional anti-phytochrome single-chain Fv protein in transgenic tobacco. Bio/Technology 10: 790-794
38. Tavladoraki P., Benvenuto E., Trinca S., De Martinis D., Cattaneo A. and Galeffi P. (1993) Transgenic plants expressing a functional single-chain Fv antibody are specifically protected from virus attack. Nature 366: 469-472
39. Zimmermann S., Schillberg S., Liao Y. C. and Fischer R. (1998) Intracellular expression of TMV-specific single-chain Fv fragments leads to improved virus resistance in Nicotiana tabacum. Mol. Breed. 4: 369-379
40. Schouten A., Roosien J., Engelen F. A. van, Jong G. A. M. de, Borst Vrenssen A. W. M., Zilverentant J. F. et al. (1996) The C-terminal KDEL sequence increases the expression level of a single-chain antibody designed to be targeted to both the cytosol and the secretory pathway in transgenic tobacco. Plant Mol. Biol. 30: 781-793
41. Fiedler U., Philips J., Artsaenko O. and Conrad U. (1997) Optimisation of scFv antibody production in transgenic plants. Immunotechnology 3: 205-216
42. Fischer R., Schumann D., Zimmermann S., Drossard J., Sack M. and Schillberg S. (1999) Expression and characterization of bispecific single chain Fv fragments produced in transgenic plants. Eur. J. Biochem. 262: 810-816
43. Benvenuto E., Ordas R. J., Tavazza R., Ancora G, Biocca S., Cattaneo A. et al. (1991) 'Phytoantibodies': a general vector for the expression of immunoglobulin domains in transgenic plants. Plant Mol. Biol. 17: 865-874
44. Francisco J. A., Gawlak S. L., Miller M., Bathe J., Russell D., Chace D. et al. (1997) Expression and characterization of bryodin 1 and a bryodin 1-based single-chain immunotoxin from tobacco cell culture. Bioconjug. Chem. 8: 708-713
45. Spiegel H., Schillberg S., Sack M., Holzem A., Nähring J., Monecke M. et al. (1999) Expression of antibody fusion proteins in the cytoplasm and ER of plant cells. Plant Sci. 149: 63-71
46. Burton D. (1995) Phage display. Immunotechnology 1: 87-94
47. Griffiths A. and Duncan A. (1998) Strategies for selection of antibodies by phage display. Curr. Opin. Biotechnol. 9: 102-108
48. Knappik A., Ge L. M., Honegger A., Pack P., Fischer M., Wellnhofer G. et al. (2000) Fully synthetic human combinatorial antibody libraries (HuCAL) based on modular consensus frameworks and CDRs randomized with trinucleotides. J. Mol. Biol. 296: 57-86
49. Sidhu S. S. (2000) Phage display in pharmaceutical biotechnology. Curr. Opin. Biotechnol. 11: 610-616
50. Kay R., Chan A., Daly M. and McPherson J. (1987) Duplication of CaMV-35S promoter sequences creates a strong enhancer for plant genes. Science 236: 1299-1302
51. McElroy D. and Brettel R. I. S. (1994) Foreign gene expression in transgenic cereals. Trends Biotechnol. 12: 62-68
52. Vain P., Finer K. R., Engler D. E., Pratt R. C. and Finer J. J. (1996) Intron-mediated enhancement of gene expression in maize (Zea mays L) and bluegrass (Poa pratensis L). Plant Cell Rep. 15: 489-494
53. Bilan R., Futterer J. and Sautter C. (1999) Transformation of cereals. Genet. Eng. 21: 113-157
54. Artsaenko O., Kettig B., Fiedler U., Conrad U. and Düring K. (1998) Potato tubers as a biofactory for recombinant antibodies. Mol. Breed. 4: 313-319
55. Stoger E., Williams S., Keen D. and Christou P. (1999) Constitutive versus seed specific expression in transgenic wheat: temporal and spatial control. Transgen. Res. 8: 73-82
56. Futterer J. and Hohn T. (1996) Translation in plants - rules and exceptions. Plant Mol. Biol. 32: 159-189
57. Gallie D. R. (1996) Translational control of cellular and viral mRNAs. Plant Mol. Biol. 32: 145-158
58. Hiatt A., Cafferkey R. and Bowdish K. (1989). Production of antibodies in transgenic plants. Nature 342: 76-78
59. Schillberg S., Zimmermann S., Voss A. and Fischer R. (1999) Apoplastic and cytosolic expression of full-size antibodies and antibody fragments in Nicotiana tabacum. Transgen. Res. 8: 255-263
60. De Jaeger G., Buys E., Eeckhout D., De Wilde C., Jacobs A., Kapila J. et al. (1998). High-level accumulation of single-chain variable fragments in the cytosol of transgenic Petunia hybrida. Eur. J. Biochem. 259: 1-10
61. Schouten A., Rossien J., Bakker J. and Schots A. (2002) Formation of disulfide bridges by a single-chain Fv antibody in the reducing ectopic environment of the plant cytosol. J. Biol. Chem. 277: 19339-19345
62. Conrad U. and 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: 101-109
63. Munro S. and Pelham H. R. (1987) A C-terminal signal prevents secretion of luminal ER proteins. Cell 48: 899-907
64. Fischer R., Liao Y. C. and Drossard J. (1999) Affinity-purification of a TMV-specific recombinant full-size antibody from a transgenic tobacco suspension culture. J. Immunol. Methods 226: 1-10
65. Staub J. M., Garcia B., Graves J., Hajdukiewicz P. T., Hunter P., Nehra N. et al. (2000) High-yield production of a human therapeutic protein in tobacco chloroplasts. Nat. Biotechnol. 18: 333-338
66. Daniell H., Khan M. S. and Allison L. (2002) Milestones in chloroplast genetic engineering: an environmentally friendly era in biotechnology. Trends Plant Sci. 7: 84-91
67. Horsch R., Fry J. E., Hoffman N., Eicholtz D., Rogers S. and Fraley R. (1985) A simple and general method for transferring genes into plants. Science 227: 1229-1231
68. Christou P. (1993) Particle gun-mediated transformation. Curr. Opin. Biotechnol. 4: 135-141
69. Khoudi H., Laberge S., Ferullo J. M., Bazin R., Darveau A., Castonguay Y. et al. (1999) Production of a diagnostic monoclonal antibody in perennial alfalfa plants. Biotechnol. Bioeng. 64: 135-143
70. Eeckhout D., Fiers E., Sienaert R., Snoeck V., Depicker A. and De Jaeger G. (2000) Isolation and characterization of recombinant antibody fragments against CDC2a from Arabidopsis thaliana. Eur. J. Biochem. 267: 6775-6783
71. Perrin Y., Vaquero C., Gerrard I., Sack M., Drossard J., Stöger E. et al. (2000) Transgenic pea seeds as bioreactors for the production of single chain Fv antibody fragment (scFv) used in cancer diagnosis and therapy. Mol. Breed. 6: 345-352
72. Saalbach I., Giersberg M. and Conrad U. (2001) High-level expression of a single-chain Fv fragment (scFv) antibody in transgenic pea seeds. J. Plant Physiol. 158: 529-533
73. Zeitlin L., Olmsted S. S., Moench T. R., Co M. S., Martinell B. J., Paradkar V. M. et al. (1998) A humanized monoclonal antibody produced in transgenic plants for immunoprotection of the vagina against genital herpes. Nat. Biotechnol. 16: 1361-1364
74. Torres E., Vaquero C., Nicholson L., Sack M., Stöger E., Drossard J. et al. (1999) Rice cell culture as an alternative production system for functional diagnostic and therapeutic antibodies. Transgen. Res. 8: 441-449
75. Stöger E., Vaquero C., Torres E., Sack M., Nicholson L., Drossard J. et al. (2000) Cereal crops as viable production and storage systems for pharmaceutical scFv antibodies. Plant Mol. Biol. 42: 583-590
76. Kapila J., De Rycke R., Montagu M. van and Angenon G. (1996) An Agrobacterium-mediated transient gene expression system for intact leaves. Plant Sci. 122: 101-108
77. Scholthof H., Scholthof K. and Jackson A. (1996) Plant virus gene vectors for transient expression of foreign proteins in plants. Annu. Rev. Phytopathol. 34: 299-323
78. Porta C. and Lomonossoff G. P. (2002) Viruses as vectors for the expression of foreign sequences in plants. Biotechnol. & Genet. Eng. Rev. 19: 245-291
79. Hendy S., Chen Z. C., Barker H., Santa Cruz S., Chapman S., Torrance L. et al. (1999) Rapid production of single-chain Fv fragments in plants using a potato virus X episomal vector. J. Immunol. Methods 231: 137-146
80. Franconi R., Roggero P., Pirazzi P., Arias F. J., Desiderio A., Bitti O. et al. (1999) Functional expression in bacteria and plants of an scFv antibody fragment against tospoviruses. Immunotechnology 4: 189-201
81. McCormick A. A., Kumagai M. H., Hanley K., Turpen T. H., Hakim I., Grill L. K. et al. (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: 703-708
82. Verch T., Yusibov V. and Koprowski H. (1998) Expression and assembly of a full-length monoclonal antibody in plants using a plant virus vector. J. Immunol. Methods 220: 69-75
83. Kumagai M. H., Donson J., Della-Cioppa G. and Grill L. K. (2000) Rapid, high-level expression of glycosylated rice alpha-amylase in transfected plants by an RNA viral vector. Gene 245: 169-174
84. Koncz C. and Schell J. (1986) The promoter of TL-DNA gene 5 controls the tissue specific expression of chimeric genes carried by a novel type of Agrobacterium binary vector. Mol. Gen. Genet. 204: 383-396
85. Lindsey K. and Jones M. G. K. (1987) Transient gene expression in electroporated protoplasts and intact cells of sugar beet. Plant Mol. Biol. 10: 43-52
86. Porta C. and Lomonossoff G. P. (1996) Use of viral replicons for the expression of genes in plants. Mol. Biotechnol. 5: 209-221
87. An G. (1985) High efficiency transformation of cultured tobacco cells. Plant Physiol. 79: 568-570
88. Carpita N., Sabularse D., Montezinos D. and Delmer D. P. (1979) Determination of the pore size of cell walls of living plant cells. Science 205: 1144-1147
89. Magnuson N. S., Linzmaier P. M., Reeves R., An G., Hay-Glass K. and Lee J. M. (1998) Secretion of biologically active human interleukin-2 and interleukin-4 from genetically modified tobacco cells in suspension culture. Protein Express. Purif. 13: 45-52
90. Moloney M. M. and Holbrook L. A. (1997) Subcellular targeting and purification of recombinant proteins in plant production systems. Biotechnol. Genet. Eng. Rev. 14: 321-336
91. Sharp J. and Doran P. (2001) Characterization of monoclonal antibody fragments produced by plant cells. Biotechnol. Bioeng. 73: 338-346
92. Russell D. and Fuller J. (2000) Method for producing antibodies in plant cells. United States Patent 6,080,560, Monsanto Company, St. Louis, Mo.
93. Doran P. M. (2000) Foreign protein production in plant tissue cultures. Curr. Opin. Biotechnol. 11: 199-204
94. Terashima M., Ejiri Y., Hashikawa N. and Yoshida H. (1999) Effect of osmotic pressure on human αa1-antitrypsin production by plant cell culture. Biochem. Eng. J. 4: 31-36
95. Terashima M., Murai Y., Kawamura M., Nakanishi S., Stoltz T., Chen L. et al. (1999) Production of functional human αa1-antitrypsin by plant cell culture. Appl. Microbiol. Biotechnol. 52: 516-523
96. Stöger E., Sack M., Perrin Y., Vaquero C., Torres E., Twyman R. M. et al. (2002) Practical considerations for pharmaceutical antibody production in different crop systems. Mol. Breed. 9: 149-158
97. Verwoerd T. C., Paridon P. A. van, Ooyen A. J. J. van, Lent J. W. M. van, Hoekema A. and Pen J. (1995) Stable accumulation of Aspergillus niger phytase in transgenic tobacco leaves. Plant Physiol. 109: 1199-1205
98. Ziegler M., Thomas S. and Danna K. (2000) Accumulation of a thermostable endo-1,4-b-D-glucanase in the apoplast of Arabidopsis thaliana leaves. Mol. Breeding 6: 37-46
99. Evangelista R. L., Kusnadi A. R., Howard J. A. and Nikolov Z. L. (1998) Process and economic evaluation of the extraction and purification of recombinant beta-glucuronidase from transgenic corn. Biotechnol. Prog. 14: 607-614
100. Borisjuk N. V., Borisjuk L. G., Logendra S., Petersen F., Gleba Y. and Raskin I. (1999) Production of recombinant proteins in plant root exudates. Nat. Biotechnol. 17: 466-469
101. Gleba D., Borisjuk N. V., Borisjuk L. G., Kneer R., Poulev A., Sarzhinskaya M. et al. (1999) Use of plant roots for phytoremediation and molecular farming. Proc. Natl. Acad. Sci. USA 96: 5973-5977
102. Komarnytsky S., Borisjuk N. V., Borisjuk L. G., Alam M. Z. and Raskin I. (2000) Production of recombinant proteins in tobacco guttation fluid. Plant Physiol. 124: 927-933
103. Sheen S. (1983) Biomass and chemical composition of tobacco plants under high density growth. Beitr Tabakforsch. Int. 12: 35-42
104. Cramer C. L., Weissenborn D. L., Oishi K. K., Grabau E. A., Bennett S., Ponce E. et al. (1996) Bioproduction of human enzymes in transgenic tobacco. Ann. NY Acad. Sci. 792: 62-71
105. Ma J. K., Hikmat B. Y., Wycoff K., Vine N. D., Chargelegue D., Yu L. et al. (1998) Characterization of a recombinant plant monoclonal secretory antibody and preventive immunotherapy in humans. Nat. Med. 4: 601-606
106. Bruyns A. M., De Jaeger G., De Neve M., De Wilde C., Van Montagu M. and Depicker A. (1996) Bacterial and plant-produced scFv proteins have similar antigen-binding properties. FEBS Lett. 386: 5-10
107. Vine N. D., Drake P., Hiatt A. and Ma J. K. C. (2001) Assembly and plasma membrane targeting of recombinant immunoglobulin chains in plants with a murine immunoglobulin transmembrane sequence. Plant Mol. Biol. 45: 159-167