Production of different glycosylation variants of the tumour-targeting mAb H10 in Nicotiana benthamiana: Influence on expression yield and antibody degradation

Transgenic Research

Volumn 21, Issue 5, 2012, Pages 1005-1021

  Lombardi, Raffaele ^a   Donini, Marcello ^a   Villani, Maria Elena ^a   Brunetti, Patrizia ^a,d   Fujiyama, Kazuhito ^b   Kajiura, Hiroyuki ^b   Paul, Matthew ^c   Ma, Julian K C ^c   Benvenuto, Eugenio ^a  

^a ENEA   (Italy)

^b OSAKA UNIVERSITY   (Japan)

^c ST GEORGE'S UNIVERSITY OF LONDON   (United Kingdom)

^d SAPIENZA UNIVERSITY OF ROME   (Italy)

Author keywords

Agro infiltration; Antibody purification; Gene silencing suppressor; Glycosylation; Plant made biopharmaceuticals; Proteolysis

Indexed keywords

CANCER ANTIBODY; IMMUNOGLOBULIN F(AB) FRAGMENT; IMMUNOGLOBULIN G; MONOCLONAL ANTIBODY; POLYSACCHARIDE;

ARTICLE; BIOSYNTHESIS; ENDOPLASMIC RETICULUM; GENE EXPRESSION REGULATION; GENETICS; GLYCOSYLATION; HUMAN; ISOLATION AND PURIFICATION; METABOLISM; MOLECULAR CLONING; PLANT LEAF; POLYACRYLAMIDE GEL ELECTROPHORESIS; PROTEIN ENGINEERING; PROTEIN STABILITY; PROTOPLAST; RHIZOBIUM RADIOBACTER; RNA INTERFERENCE; SITE DIRECTED MUTAGENESIS; SUPPRESSOR GENE; TOBACCO; TRANSGENIC PLANT;

AGROBACTERIUM TUMEFACIENS; ANTIBODIES, MONOCLONAL; ANTIBODIES, NEOPLASM; CLONING, MOLECULAR; ELECTROPHORESIS, POLYACRYLAMIDE GEL; ENDOPLASMIC RETICULUM; GENE EXPRESSION REGULATION, PLANT; GENES, SUPPRESSOR; GLYCOSYLATION; HUMANS; IMMUNOGLOBULIN FAB FRAGMENTS; IMMUNOGLOBULIN G; MUTAGENESIS, SITE-DIRECTED; PLANT LEAVES; PLANTS, GENETICALLY MODIFIED; POLYSACCHARIDES; PROTEIN ENGINEERING; PROTEIN STABILITY; PROTOPLASTS; RNA INTERFERENCE; TOBACCO;

NICOTIANA BENTHAMIANA;

EID: 84865978982     PISSN: 09628819     EISSN: None     Source Type: Journal    
DOI: 10.1007/s11248-012-9587-1     Document Type: Article

References (42)

1. Bardor M, Faveeuw C, Fitchette AC, Gilbert D, Galas L, Trottein F, Faye L, Lerouge P (2003) Immunoreactivity in mammals of two typical plant glyco-epitopes, core alpha (1, 3)-fucose and core xylose. Glycobiology 13(6): 427-434.
2. Bencúrová M, Hemmer W, Focke-Tejkl M, Wilson IB, Altmann F (2004) Specificity of IgG and IgE antibodies against plant and insect glycoprotein glycans determined with artificial glycoforms of human transferrin. Glycobiology 14(5): 457-466.
3. Castilho A, Strasser R, Stadlmann J, Grass J, Jez J, Gattinger P, Kunert R, Quendler H, Pabst M, Leonard R, Altmann F, Steinkellner H (2010) In planta protein sialylation through overexpression of the respective mammalian pathway. J Biol Chem 285(21): 15923-15930.
4. Cox KM, Sterling JD, Regan JT, Gasdaska JR, Frantz KK, Peele CG, Black A, Passmore D, Moldovan-Loomis C, Srinivasan M, Cuison S, Cardarelli PM, Dickey LF (2006) Glycan optimization of a human monoclonal antibody in the aquatic plant Lemna minor. Nat Biotechnol 24(12): 1591-1597.
5. Floss DM, Sack M, Stadlmann J, Rademacher T, Scheller J, Stöger E, Fischer R, Conrad U (2008) Biochemical and functional characterization of anti-HIV antibody-ELP fusion proteins from transgenic plants. Plant Biotechnol J 6(4): 379-391.
6. Floss DM, Sack M, Arcalis E, Stadlmann J, Quendler H, Rademacher T, Stoger E, Scheller J, Fischer R, Conrad U (2009) Influence of elastin-like peptide fusions on the quantity and quality of a tobacco-derived human immunodeficiency virus-neutralizing antibody. Plant Biotechnol J 7(9): 899-913.
7. Forthal DN, Gach JS, Landucci G, Jez J, Strasser R, Kunert R, Steinkellner H (2010) Fc-glycosylation influences Fcγ receptor binding and cell-mediated anti-HIV activity of monoclonal antibody 2G12. J Immunol 185(11): 6876-6882.
8. Fujiyama K, Furukawa A, Katsura A, Misaki R, Omasa T, Seki T (2007) Production of mouse monoclonal antibody with galactose-extended sugar chain by suspension cultured tobacco BY2 cells expressing human beta(1, 4)-galactosyltransferase. Biochem Biophys Res Commun 358(1): 85-91.
9. Gill SC, von Hippel PH (1989) Calculation of protein extinction coefficients from amino acid sequence data. Anal Biochem 182(2): 319-326.
10. Givol D, Zakut R, Effron K, Rechavi G, Ram D, Cohen JB (1981) Diversity of germ-line immunoglobulin VH genes. Nature 292(5822): 426-430.
11. Gomord V, Fitchette AC, Menu-Bouaouiche L, Saint-Jore-Dupas C, Plasson C, Michaud D, Faye L (2010) Plant-specific glycosylation patterns in the context of therapeutic protein production. Plant Biotechnol J 8(5): 564-587.
12. Goulet C, Khalf M, Sainsbury F, D'Aoust MA, Michaud D (2011) A protease activity-depleted environment for heterologous proteins migrating towards the leaf cell apoplast. Plant Biotechnol J, doi: 10. 1111/j. 1467-7652. 2011. 00643. x [Epub ahead of print].
13. Hadlington J, Santoro A, Nuttal J, Denecke J, Ma JK-C, Vitale A, Frigerio L (2003) The C-terminal extension of a hybrid immunoglobulin A/G heavy chain is responsible for its Golgi-mediated sorting to the vacuole. Mol Biol Cell 14(6): 2592-2602.
14. Jung ST, Reddy ST, Kang TH, Borrok MJ, Sandlie I, Tucker PW, Georgiou G (2010) Aglycosylated IgG variants expressed in bacteria that selectively bind FcgammaRI potentiate tumor cell killing by monocyte-dendritic cells. Proc Natl Acad Sci USA 107(2): 604-609.
15. Kajiura H, Seki T, Fujiyama K (2010) Arabidopsis thaliana ALG3 mutant synthesizes immature oligosaccharides in the ER and accumulates unique N-glycans. Glycobiology 20(6): 736-751.
16. Kaulfürst-Soboll H, Rips S, Koiwa H, Kajiura H, Fujiyama K, von Schaewen A (2011) Reduced immunogenicity of Arabidopsis hgl1 mutant N-glycans caused by altered accessibility of xylose and core fucose epitopes. J Biol Chem 286: 22955-22964.
17. Kayser V, Chennamsetty N, Voynov V, Forrer K, Helk B, Trout BL (2011) Glycosylation influences on the aggregation propensity of therapeutic monoclonal antibodies. Biotechnol J 6(1): 38-44.
18. Kogelberg H, Tolner B, Sharma SK, Lowdell MW, Qureshi U, Robson M, Hillyer T, Pedley RB, Vervecken W, Contreras R, Begent RH, Chester KA (2007) Clearance mechanism of a mannosylated antibody-enzyme fusion protein used in experimental cancer therapy. Glycobiol 17(1): 36-45.
19. Lombardi R, Villani ME, Di Carli M, Brunetti P, Benvenuto E, Donini M (2010) Optimisation of the purification process of a tumour-targeting antibody produced in N. benthamiana using vacuum-agro-infiltration. Transgenic Res 19(6): 1083-1097.
20. Loos A, van Droogenbroeck B, Hillmer S, Grass J, Kunert R, Cao J, Robinson DG, Depicker A, Steinkellner H (2011) Production of monoclonal antibodies with a controlled N-glycosylation pattern in seeds of Arabidopsis thaliana. Plant Biotechnol J 9(2): 179-192.
21. Marusic C, Nuttall J, Buriani G, Lico C, Lombardi R, Baschieri S, Benvenuto E, Frigerio L (2007) Expression, intracellular targeting and purification of HIV Nef variants in tobacco cells. BMC Biotechnol 7: 12.
22. Merril CR, Dunau ML, Goldman D (1981) A rapid sensitive silver stain for polypeptides in polyacrylamide gels. Anal Biochem 110(1): 201-207.
23. Misaki R, Kimura Y, Fujiyama K, Seki T (2001) Glycoproteins secreted from suspension-cultured tobacco BY2 cells have distinct glycan structures from intracellular glycoproteins. Biosci Biotechnol Biochem 65(11): 2482-2488.
24. Nuttall J, Ma JK, Frigerio L (2005) A functional antibody lacking N-linked glycans is efficiently folded, assembled and secreted by tobacco mesophyll protoplasts. Plant Biotechnol J 3(5): 497-504.
25. Pedrazzini E, Giovinazzo G, Bielli A, de Virgilio M, Frigerio L, Pesca M, Faoro F, Bollini R, Ceriotti A, Vitale A (1997) Protein quality control along the route to the plant vacuole. Plant Cell 9(10): 1869-1880.
26. Petruccelli S, Otegui MS, Lareu F, Tran Dinh O, Fitchette AC, Circosta A, Rumbo M, Bardor M, Carcamo R, Gomord V, Beachy RN (2006) A KDEL-tagged monoclonal antibody is efficiently retained in the endoplasmic reticulum in leaves, but is both partially secreted and sorted to protein storage vacuoles in seeds. Plant Biotechnol J 4(5): 511-527.
27. Rademacher T, Sack M, Arcalis E, Stadlmann J, Balzer S, Altmann F, Quendler H, Stiegler G, Kunert R, Fischer R, Stoger E (2008) Recombinant antibody 2G12 produced in maize endosperm efficiently neutralizes HIV-1 and contains predominantly single-GlcNAc N-glycans. Plant Biotechnol J 6(2): 189-201.
28. Rodríguez M, Ramírez NI, Ayala M, Freyre F, Pérez 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(2): 188-194.
29. Sainsbury F, Sack M, Stadlmann J, Quendler H, Fischer R, Lomonossoff GP (2010) Rapid transient production in plants by replicating and non-replicating vectors yields high quality functional anti-HIV antibody. PLoS One 5: e13976.
30. Saint-Jore-Dupas C, Faye L, Gomord V (2007) From planta to pharma with glycosylation in the toolbox. Trends Biotechnol 25(7): 317-323.
31. Schähs M, Strasser R, Stadlmann J, Kunert R, Rademacher T, Steinkellner H (2007) Production of a monoclonal antibody in plants with a humanized N-glycosylation pattern. Plant Biotechnol J 5(5): 657-663.
32. Schillberg S, Fischer R, Emans N (2003) Molecular farming of recombinant antibodies in plants. Cell Mol Life Sci 60(3): 433-445.
33. 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-alpha(1, 3)-fucose residues. Plant Biotechnol J 2(4): 279-287.
34. Strasser R, Stadlmann J, Schähs M, Stiegler G, Quendler H, Mach L, Glössl J, Weterings K, Pabst M, Steinkellner H (2008) Generation of glyco-engineered Nicotiana benthamiana for the production of monoclonal antibodies with a homogeneous human-like N-glycan structure. Plant Biotechnol J 6: 392-402.
35. Strasser R, Castilho A, Stadlmann J, Kunert R, Quendler H, Gattinger P, Jez J, Rademacher T, Altmann F, Mach L, Steinkellner H (2009) Improved virus neutralization by plant-produced anti-HIV antibodies with a homogeneous β1, 4-galactosylated N-glycan profile. J Biol Chem 284(31): 20479-20485.
36. Tavladoraki P, Girotti A, Donini M, Arias FJ, Mancini C, Morea V, Chiaraluce R, Consalvi V, Benvenuto E (1999) A single-chain antibody fragment is functionally expressed in the cytoplasm of both Escherichia coli and transgenic plants. Eur J Biochem 262: 617-624.
37. Tekoah Y, Ko K, Koprowski H, Harvey DJ, Wormald MR, Dwek RA, Rudd PM (2004) Controlled glycosylation of therapeutic antibodies in plants. Arch Biochem Biophys 426: 266-278.
38. 2. Anal Biochem 193: 90-100.
39. 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: 449-457.
40. Twyman RM, Schillberg S, Fischer R (2005) Transgenic plants in the biopharmaceutical market. Exp Opin Emerg Drugs 10: 185-218.
41. Vézina LP, Faye L, Lerouge P, D'Aoust MA, Marquet-Blouin E, Burel C, Lavoie PO, Bardor M, Gomord V (2009) Transient co-expression for fast and high-yield production of antibodies with human-like N-glycans in plants. Plant Biotechnol J 7: 442-455.
42. Villani ME, Morgun B, Brunetti P, Marusic C, Lombardi R, Pisoni I, Bacci C, Desiderio A, Benvenuto E, Donini M (2009) Plant pharming of a full-sized, tumour-targeting antibody using different expression strategies. Plant Biotechnol J 7: 59-72.