Plant-Made Antibodies: Properties and Therapeutic Applications

Author(s): Tatiana V. Komarova, Ekaterina V. Sheshukova, Yuri L. Dorokhov*.

Journal Name: Current Medicinal Chemistry

Volume 26 , Issue 3 , 2019

  Journal Home
Translate in Chinese
Become EABM
Become Reviewer

Abstract:

Background: A cost-effective plant platform for therapeutic monoclonal antibody production is both flexible and scalable. Plant cells have mechanisms for protein synthesis and posttranslational modification, including glycosylation, similar to those in animal cells. However, plants produce less complex and diverse Asn-attached glycans compared to animal cells and contain plant-specific residues. Nevertheless, plant-made antibodies (PMAbs) could be advantageous compared to those produced in animal cells due to the absence of a risk of contamination from nucleic acids or proteins of animal origin.

Objective: In this review, the various platforms of PMAbs production are described, and the widely used transient expression system based on Agrobacterium-mediated delivery of genetic material into plant cells is discussed in detail.

Results: We examined the features of and approaches to humanizing the Asn-linked glycan of PMAbs. The prospects for PMAbs in the prevention and treatment of human infectious diseases have been illustrated by promising results with PMAbs against human immunodeficiency virus, rotavirus infection, human respiratory syncytial virus, rabies, anthrax and Ebola virus. The pre-clinical and clinical trials of PMAbs against different types of cancer, including lymphoma and breast cancer, are addressed.

Conclusion: PMAb biosafety assessments in patients suggest that it has no side effects, although this does not completely remove concerns about the potential immunogenicity of some plant glycans in humans. Several PMAbs at various developmental stages have been proposed. Promise for the clinical use of PMAbs is aimed at the treatment of viral and bacterial infections as well as in anti-cancer treatment.

Keywords: Plant-produced antibody, monoclonal antibody, immunotherapy, therapeutic antibody, antibody glycosylation, PMab.

[1]
Gupta, S.K.; Shukla, P. Microbial platform technology for recombinant antibody fragment production: A review. Crit. Rev. Microbiol., 2017, 43(1), 31-42.
[2]
Dorokhov, Y.L.; Sheshukova, E.V.; Kosobokova, E.N.; Shindyapina, A.V.; Kosorukov, V.S.; Komarova, T.V. Functional role of carbohydrate residues in human immunoglobulin g and therapeutic monoclonal antibodies. Biochemistry (Mosc.), 2016, 81(8), 835-857.
[3]
Niwa, R.; Satoh, M. The current status and prospects of antibody engineering for therapeutic use: focus on glycoengineering technology. J. Pharm. Sci., 2015, 104(3), 930-941.
[4]
Kunert, R.; Casanova, E. Recent advances in recombinant protein production: BAC-based expression vectors, the bigger the better. Bioengineered, 2013, 4(4), 258-261.
[5]
Walsh, G. Biopharmaceutical benchmarks 2014. Nat. Biotechnol., 2014, 32(10), 992-1000.
[6]
Jennewein, M.F.; Alter, G. The immunoregulatory roles of antibody glycosylation. Trends Immunol., 2017, 38(5), 358-372.
[7]
Hossler, P. Protein glycosylation control in mammalian cell culture: Past precedents and contemporary prospects. Adv. Biochem. Eng. Biotechnol., 2012, 127, 187-219.
[8]
Liu, L. Antibody glycosylation and its impact on the pharmacokinetics and pharmacodynamics of monoclonal antibodies and Fc-fusion proteins. J. Pharm. Sci., 2015, 104(6), 1866-1884.
[9]
Holtz, B.R.; Berquist, B.R.; Bennett, L.D.; Kommineni, V.J.M.; Munigunti, R.K.; White, E.L.; Wilkerson, D.C.; Wong, K-Y.I.; Ly, L.H.; Marcel, S. Commercial-scale biotherapeutics manufacturing facility for plant-made pharmaceuticals. Plant Biotechnol. J., 2015, 13(8), 1180-1190.
[10]
Qiu, X.; Wong, G.; Audet, J.; Bello, A.; Fernando, L.; Alimonti, J.B.; Fausther-Bovendo, H.; Wei, H.; Aviles, J.; Hiatt, E.; Johnson, A.; Morton, J.; Swope, K.; Bohorov, O.; Bohorova, N.; Goodman, C.; Kim, D.; Pauly, M.H.; Velasco, J.; Pettitt, J.; Olinger, G.G.; Whaley, K.; Xu, B.; Strong, J.E.; Zeitlin, L.; Kobinger, G.P. Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp. Nature, 2014, 514(7520), 47-53.
[11]
Hiatt, A.; Pauly, M.; Whaley, K.; Qiu, X.; Kobinger, G.; Zeitlin, L. The emergence of antibody therapies for Ebola. Hum. Antibodies, 2015, 23(3-4), 49-56.
[12]
Lomonossoff, G.P.; D’Aoust, M-A. Plant-produced biopharmaceuticals: A case of technical developments driving clinical deployment. Science, 2016, 353(6305), 1237-1240.
[13]
Strasser, R. Plant protein glycosylation. Glycobiology, 2016, 26(9), 926-939.
[14]
Strasser, R. Biological significance of complex N-glycans in plants and their impact on plant physiology. Front. Plant Sci., 2014, 5, 363.
[15]
Hiatt, A.; Whaley, K.J.; Zeitlin, L. Plant-derived monoclonal antibodies for prevention and treatment of infectious disease. Microbiol. Spectr., 2014, 2(1), AID-0004-AID-2012.
[16]
Takeyama, N.; Kiyono, H.; Yuki, Y. Plant-based vaccines for animals and humans: recent advances in technology and clinical trials. Ther. Adv. Vaccines, 2015, 3(5-6), 139-154.
[17]
Tschofen, M.; Knopp, D.; Hood, E.; Stöger, E. Plant molecular Farming: Much more than medicines. Annu. Rev. Anal. Chem. (Palo Alto, Calif.), 2016, 9(1), 271-294.
[18]
De Muynck, B.; Navarre, C.; Boutry, M. Production of antibodies in plants: status after twenty years. Plant Biotechnol. J., 2010, 8(5), 529-563.
[19]
Whaley, K.J.; Morton, J.; Hume, S.; Hiatt, E.; Bratcher, B.; Klimyuk, V.; Hiatt, A.; Pauly, M.; Zeitlin, L. Emerging antibody-based products. Curr. Top. Microbiol. Immunol., 2014, 375, 107-126.
[20]
Hiatt, A.; Cafferkey, R.; Bowdish, K. Production of antibodies in transgenic plants. Nature, 1989, 342(6245), 76-78.
[21]
De Muynck, B.; Navarre, C.; Boutry, M. Production of antibodies in plants: status after twenty years. Plant Biotechnol. J., 2010, 8(5), 529-563.
[22]
Gasdaska, J.; Spencer, D.; Dickey, L. Advantages of therapeutic protein production in the aquatic plant Lemna Bio- Process. J., 2003, 2 49-56
[23]
Yamamoto, Y.T.; Rajbhandari, N.; Lin, X.; Bergmann, B.A.; Nishimura, Y.; Stomp, A-M. Genetic Transformation of Duckweed Lemna gibba and Lemna minor. In Vitro Cell. Dev. Biol. Plant, 2001, 37, 349-353.
[24]
Cox, K.M.; Sterling, J.D.; Regan, J.T.; Gasdaska, J.R.; Frantz, K.K.; Peele, C.G.; Black, A.; Passmore, D.; Moldovan-Loomis, C.; Srinivasan, M.; Cuison, S.; Cardarelli, P.M.; Dickey, L.F. Glycan optimization of a human monoclonal antibody in the aquatic plant Lemna minor. Nat. Biotechnol., 2006, 24(12), 1591-1597.
[25]
Stoger, E.; Fischer, R.; Moloney, M.; Ma, J.K-C. Plant molecular pharming for the treatment of chronic and infectious diseases. Annu. Rev. Plant Biol., 2014, 65, 743-768.
[26]
Hensel, G.; Floss, D.M.; Arcalis, E.; Sack, M.; Melnik, S.; Altmann, F.; Rutten, T.; Kumlehn, J.; Stoger, E.; Conrad, U. Transgenic production of an anti HIV antibody in the barley endosperm. PLoS One, 2015, 10(10), e0140476.
[27]
Vamvaka, E.; Twyman, R.M.; Murad, A.M.; Melnik, S.; Teh, A.Y-H.; Arcalis, E.; Altmann, F.; Stoger, E.; Rech, E.; Ma, J.K.C.; Christou, P.; Capell, T. Rice endosperm produces an underglycosylated and potent form of the HIV-neutralizing monoclonal antibody 2G12. Plant Biotechnol. J., 2016, 14(1), 97-108.
[28]
Gleba, Y.Y.; Tusé, D.; Giritch, A. Plant viral vectors for delivery by Agrobacterium. Curr. Top. Microbiol. Immunol., 2014, 375, 155-192.
[29]
Komarova, T.V.; Baschieri, S.; Donini, M.; Marusic, C.; Benvenuto, E.; Dorokhov, Y.L. Transient expression systems for plant-derived biopharmaceuticals. Expert Rev. Vaccines, 2010, 9(8), 859-876.
[30]
Nandi, S.; Kwong, A.T.; Holtz, B.R.; Erwin, R.L.; Marcel, S.; McDonald, K.A. Techno-economic analysis of a transient plant-based platform for monoclonal antibody production. MAbs, 2016, 8(8), 1456-1466.
[31]
Lam, E. Analysis of tissue-specific elements in the CaMV 35S promoter. Results Probl. Cell Differ., 1994, 20, 181-196.
[32]
Sainsbury, F.; Lavoie, P-O.; D’Aoust, M-A.; Vézina, L-P.; Lomonossoff, G.P. Expression of multiple proteins using full-length and deleted versions of cowpea mosaic virus RNA-2. Plant Biotechnol. J., 2008, 6(1), 82-92.
[33]
Marillonnet, S.; Thoeringer, C.; Kandzia, R.; Klimyuk, V.; Gleba, Y. Systemic Agrobacterium tumefaciens-mediated transfection of viral replicons for efficient transient expression in plants. Nat. Biotechnol., 2005, 23(6), 718-723.
[34]
Hamorsky, K.T.; Grooms-Williams, T.W.; Husk, A.S.; Bennett, L.J.; Palmer, K.E.; Matoba, N. Efficient single tobamoviral vector-based bioproduction of broadly neutralizing anti-HIV-1 monoclonal antibody VRC01 in Nicotiana benthamiana plants and utility of VRC01 in combination microbicides. Antimicrob. Agents Chemother., 2013, 57(5), 2076-2086.
[35]
Diamos, A.G.; Rosenthal, S.H.; Mason, H.S. 5′ and 3′ Untranslated Regions Strongly Enhance Performance of Geminiviral Replicons in Nicotiana benthamiana Leaves. Front. Plant Sci., 2016, 7, 200.
[36]
Huang, Z.; Phoolcharoen, W.; Lai, H.; Piensook, K.; Cardineau, G.; Zeitlin, L.; Whaley, K.J.; Arntzen, C.J.; Mason, H.S.; Chen, Q. High-level rapid production of full-size monoclonal antibodies in plants by a single-vector DNA replicon system. Biotechnol. Bioeng., 2010, 106(1), 9-17.
[37]
Giritch, A.; Marillonnet, S.; Engler, C.; van Eldik, G.; Botterman, J.; Klimyuk, V.; Gleba, Y. Rapid high-yield expression of full-size IgG antibodies in plants coinfected with noncompeting viral vectors. Proc. Natl. Acad. Sci. USA, 2006, 103(40), 14701-14706.
[38]
Garabagi, F.; McLean, M.D.; Hall, J.C. Transient and Stable Expression of Antibodies in Nicotiana SpeciesAntibody Engineering: Methods and Protocols; (2nd ed. ). , 2012. 389- 408.
[39]
Komarova, T.V.; Kosorukov, V.S.; Frolova, O.Y.; Petrunia, I.V.; Skrypnik, K.A.; Gleba, Y.Y.; Dorokhov, Y.L. Plant-made trastuzumab (herceptin) inhibits HER2/Neu+ cell proliferation and retards tumor growth. PLoS One, 2011, 6(3), e17541.
[40]
Zhang, B.; Rapolu, M.; Huang, L.; Su, W.W. Coordinate expression of multiple proteins in plant cells by exploiting endogenous kex2p-like protease activity. Plant Biotechnol. J., 2011, 9(9), 970-981.
[41]
Sainsbury, F.; Sack, M.; Stadlmann, J.; Quendler, H.; Fischer, R.; Lomonossoff, G.P. Rapid transient production in plants by replicating and non-replicating vectors yields high quality functional anti-HIV antibody. PLoS One, 2010, 5(11), e13976.
[42]
Sainsbury, F.; Thuenemann, E.C.; Lomonossoff, G.P. pEAQ: versatile expression vectors for easy and quick transient expression of heterologous proteins in plants. Plant Biotechnol. J., 2009, 7(7), 682-693.
[43]
De Neve, M.; De Loose, M.; Jacobs, A.; Van Houdt, H.; Kaluza, B.; Weidle, U.; Van Montagu, M.; Depicker, A. Assembly of an antibody and its derived antibody fragment in Nicotiana and Arabidopsis. Transgenic Res., 1993, 2(4), 227-237.
[44]
De Muynck, B.; Navarre, C.; Nizet, Y.; Stadlmann, J.; Boutry, M. Different subcellular localization and glycosylation for a functional antibody expressed in Nicotiana tabacum plants and suspension cells. Transgenic Res., 2009, 18(3), 467-482.
[45]
Komarnytsky, S.; Borisjuk, N.; Yakoby, N.; Garvey, A.; Raskin, I. Cosecretion of protease inhibitor stabilizes antibodies produced by plant roots. Plant Physiol., 2006, 141(4), 1185-1193.
[46]
Hehle, V.K.; Paul, M.J.; Roberts, V.A.; van Dolleweerd, C.J.; Ma, J.K-C. Site-targeted mutagenesis for stabilization of recombinant monoclonal antibody expressed in tobacco (Nicotiana tabacum) plants. FASEB J., 2016, 30(4), 1590-1598.
[47]
Loos, A.; Steinkellner, H. IgG-Fc glycoengineering in non-mammalian expression hosts. Arch. Biochem. Biophys., 2012, 526(2), 167-173.
[48]
Beck, A.; Wagner-Rousset, E.; Ayoub, D.; Van Dorsselaer, A.; Sanglier-Cianférani, S. Characterization of therapeutic antibodies and related products. Anal. Chem., 2013, 85(2), 715-736.
[49]
Gomord, V.; Fitchette, A-C.; Menu-Bouaouiche, L.; Saint-Jore-Dupas, C.; Plasson, C.; Michaud, D.; Faye, L. Plant-specific glycosylation patterns in the context of therapeutic protein production. Plant Biotechnol. J., 2010, 8(5), 564-587.
[50]
Liebminger, E.; Hüttner, S.; Vavra, U.; Fischl, R.; Schoberer, J.; Grass, J.; Blaukopf, C.; Seifert, G.J.; Altmann, F.; Mach, L.; Strasser, R.; Class, I. Class I alpha-mannosidases are required for N-glycan processing and root development in Arabidopsis thaliana. Plant Cell, 2009, 21(12), 3850-3867.
[51]
Strasser, R.; Mucha, J.; Schwihla, H.; Altmann, F.; Glössl, J.; Steinkellner, H. Molecular cloning and characterization of cDNA coding for beta1, 2N-acetylglucosaminyltransferase I (GlcNAc-TI) from Nicotiana tabacum. Glycobiology, 1999, 9(8), 779-785.
[52]
Fitchette, A-C.; Cabanes-Macheteau, M.; Marvin, L.; Martin, B.; Satiat-Jeunemaitre, B.; Gomord, V.; Crooks, K.; Lerouge, P.; Faye, L.; Hawes, C. Biosynthesis and immunolocalization of Lewis a-containing N-glycans in the plant cell. Plant Physiol., 1999, 121(2), 333-344.
[53]
Strasser, R.; Bondili, J.S.; Vavra, U.; Schoberer, J.; Svoboda, B.; Glössl, J.; Léonard, R.; Stadlmann, J.; Altmann, F.; Steinkellner, H.; Mach, L. A unique beta1,3-galactosyltransferase is indispensable for the biosynthesis of N-glycans containing Lewis a structures in Arabidopsis thaliana. Plant Cell, 2007, 19(7), 2278-2292.
[54]
Román, V.R.G.; Murray, J.C.; Weiner, L.M. Antibody-Dependent Cellular CytotoxicityIn: Antibody Fc: Linking Adaptive and Innate Immunity , 2014. Elsevier Inc., Chapter 1, 1-27.
[55]
Lindorfer, M.A.; Köhl, J.; Taylor, R.P. Interactions Between the Complement System and Fcγ Receptors In: Antibody Fc: Linking Adaptive and Innate Immunity, , 2014. Elsevier Inc., Chapter 3, 49-74
[56]
Sheshukova, E.V.; Komarova, T.V.; Dorokhov, Y.L. Plant Factories for the Production of Monoclonal Antibodies. Biochemistry (Mosc.), 2016, 81(10), 1118-1135.
[57]
Strasser, R.; Bondili, J.S.; Schoberer, J.; Svoboda, B.; Liebminger, E.; Glössl, J.; Altmann, F.; Steinkellner, H.; Mach, L. Enzymatic properties and subcellular localization of arabidopsis beta-N-acetylhexosaminidases. Plant Physiol., 2007, 145(1), 5-16.
[58]
Schähs, M.; Strasser, R.; Stadlmann, J.; Kunert, R.; Rademacher, T.; Steinkellner, H. Production of a monoclonal antibody in plants with a humanized N-glycosylation pattern. Plant Biotechnol. J., 2007, 5(5), 657-663.
[59]
Strasser, R.; Castilho, A.; Stadlmann, J.; Kunert, R.; Quendler, H.; Gattinger, P.; Jez, J.; Rademacher, T.; Altmann, F.; Mach, L.; Steinkellner, H. Improved virus neutralization by plant-produced anti-HIV antibodies with a homogeneous beta1,4-galactosylated N-glycan profile. J. Biol. Chem., 2009, 284(31), 20479-20485.
[60]
Strasser, R.; Stadlmann, J.; Schähs, M.; Stiegler, G.; Quendler, H.; Mach, L.; Glössl, J.; Weterings, K.; Pabst, M.; Steinkellner, H. Generation of glyco-engineered Nicotiana benthamiana for the production of monoclonal antibodies with a homogeneous human-like N-glycan structure. Plant Biotechnol. J., 2008, 6(4), 392-402.
[61]
Arnold, J.N.; Wormald, M.R.; Sim, R.B.; Rudd, P.M.; Dwek, R.A. The impact of glycosylation on the biological function and structure of human immunoglobulins. Annu. Rev. Immunol., 2007, 25, 21-50.
[62]
Altmann, F. The role of protein glycosylation in allergy. Int. Arch. Allergy Immunol., 2007, 142(2), 99-115.
[63]
Bardor, M.; Faveeuw, C.; Fitchette, A-C.; Gilbert, D.; Galas, L.; Trottein, F.; Faye, L.; Lerouge, P. Immunoreactivity in mammals of two typical plant glyco-epitopes, core α(1,3)-fucose and core xylose. Glycobiology, 2003, 13(6), 427-434.
[64]
Chargelegue, D.; Vine, N.D.; van Dolleweerd, C.J.; Drake, P.M.; Ma, J.K. A murine monoclonal antibody produced in transgenic plants with plant-specific glycans is not immunogenic in mice. Transgenic Res., 2000, 9(3), 187-194.
[65]
Jin, C.; Bencúrová, M.; Borth, N.; Ferko, B.; Jensen-Jarolim, E.; Altmann, F.; Hantusch, B.; Immunoglobulin, G. Immunoglobulin G specifically binding plant N-glycans with high affinity could be generated in rabbits but not in mice. Glycobiology, 2006, 16(4), 349-357.
[66]
Jin, C.; Altmann, F.; Strasser, R.; Mach, L.; Schähs, M.; Kunert, R.; Rademacher, T.; Glössl, J.; Steinkellner, H. A plant-derived human monoclonal antibody induces an anti-carbohydrate immune response in rabbits. Glycobiology, 2008, 18(3), 235-241.
[67]
Tusé, D.; Ku, N.; Bendandi, M.; Becerra, C.; Collins, R., Jr; Langford, N.; Sancho, S.I.; López-Díaz de Cerio, A.; Pastor, F.; Kandzia, R.; Thieme, F.; Jarczowski, F.; Krause, D.; Ma, J.K-C.; Pandya, S.; Klimyuk, V.; Gleba, Y.; Butler-Ransohoff, J.E. Clinical safety and immunogenicity of tumor-targeted, plant-made id-klh conjugate vaccines for follicular lymphoma. BioMed Res. Int., 2015, 2015, 648143.
[68]
Sriraman, R.; Bardor, M.; Sack, M.; Vaquero, C.; Faye, L.; Fischer, R.; Finnern, R.; Lerouge, P. 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., 2004, 2(4), 279-287.
[69]
Triguero, A.; Cabrera, G.; Cremata, J.A.; Yuen, C-T.; Wheeler, J.; Ramírez, N.I. 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., 2005, 3(4), 449-457.
[70]
Bosch, D.; Castilho, A.; Loos, A.; Schots, A.; Steinkellner, H. N-glycosylation of plant-produced recombinant proteins. Curr. Pharm. Des., 2013, 19(31), 5503-5512.
[71]
Loos, A.; Castilho, A. Transient glyco-engineering of n. benthamiana aiming at the synthesis of multi-antennary sialylated proteins. Methods Mol. Biol., 2015, 1321, 233-248.
[72]
Strasser, R.; Altmann, F.; Mach, L.; Glössl, J.; Steinkellner, H. Generation of Arabidopsis thaliana plants with complex N-glycans lacking beta1,2-linked xylose and core alpha1,3-linked fucose. FEBS Lett., 2004, 561(1-3), 132-136.
[73]
Nagels, B.; Van Damme, E.J.M.; Pabst, M.; Callewaert, N.; Weterings, K. Production of complex multiantennary N-glycans in Nicotiana benthamiana plants. Plant Physiol., 2011, 155(3), 1103-1112.
[74]
Strasser, R.; Stadlmann, J.; Schähs, M.; Stiegler, G.; Quendler, H.; Mach, L.; Glössl, J.; Weterings, K.; Pabst, M.; Steinkellner, H. Generation of glyco-engineered Nicotiana benthamiana for the production of monoclonal antibodies with a homogeneous human-like N-glycan structure. Plant Biotechnol. J., 2008, 6(4), 392-402.
[75]
Forthal, D.N.; Gach, J.S.; Landucci, G.; Jez, J.; Strasser, R.; Kunert, R.; Steinkellner, H. Fc-glycosylation influences Fcγ receptor binding and cell-mediated anti-HIV activity of monoclonal antibody 2G12. J. Immunol., 2010, 185(11), 6876-6882.
[76]
Holtz, B.R.; Berquist, B.R.; Bennett, L.D.; Kommineni, V.J.M.; Munigunti, R.K.; White, E.L.; Wilkerson, D.C.; Wong, K-Y.I.; Ly, L.H.; Marcel, S. Commercial-scale biotherapeutics manufacturing facility for plant-made pharmaceuticals. Plant Biotechnol. J., 2015, 13(8), 1180-1190.
[77]
Zeitlin, L.; Pettitt, J.; Scully, C.; Bohorova, N.; Kim, D.; Pauly, M.; Hiatt, A.; Ngo, L.; Steinkellner, H.; Whaley, K.J.; Olinger, G.G. Enhanced potency of a fucose-free monoclonal antibody being developed as an Ebola virus immunoprotectant. Proc. Natl. Acad. Sci. USA, 2011, 108(51), 20690-20694.
[78]
Houde, D.; Peng, Y.; Berkowitz, S.A.; Engen, J.R. Post-translational modifications differentially affect IgG1 conformation and receptor binding. Mol. Cell. Proteomics, 2010, 9(8), 1716-1728.
[79]
Bakker, H.; Bardor, M.; Molthoff, J.W.; Gomord, V.; Elbers, I.; Stevens, L.H.; Jordi, W.; Lommen, A.; Faye, L.; Lerouge, P.; Bosch, D. Galactose-extended glycans of antibodies produced by transgenic plants. Proc. Natl. Acad. Sci. USA, 2001, 98(5), 2899-2904.
[80]
Arnold, J.N.; Wormald, M.R.; Sim, R.B.; Rudd, P.M.; Dwek, R.A. The impact of glycosylation on the biological function and structure of human immunoglobulins. Annu. Rev. Immunol., 2007, 25, 21-50.
[81]
Ahmed, A.A.; Giddens, J.; Pincetic, A.; Lomino, J.V.; Ravetch, J.V.; Wang, L-X.; Bjorkman, P.J. Structural characterization of anti-inflammatory immunoglobulin G Fc proteins. J. Mol. Biol., 2014, 426(18), 3166-3179.
[82]
Li, T.; DiLillo, D.J.; Bournazos, S.; Giddens, J.P.; Ravetch, J.V.; Wang, L-X. Modulating IgG effector function by Fc glycan engineering. Proc. Natl. Acad. Sci. USA, 2017, 114(13), 3485-3490.
[83]
Zeleny, R.; Kolarich, D.; Strasser, R.; Altmann, F. Sialic acid concentrations in plants are in the range of inadvertent contamination. Planta, 2006, 224(1), 222-227.
[84]
Castilho, A.; Strasser, R.; Stadlmann, J.; Grass, J.; Jez, J.; Gattinger, P.; Kunert, R.; Quendler, H.; Pabst, M.; Leonard, R.; Altmann, F.; Steinkellner, H. In planta protein sialylation through overexpression of the respective mammalian pathway. J. Biol. Chem., 2010, 285(21), 15923-15930.
[85]
Jez, J.; Castilho, A.; Grass, J.; Vorauer-Uhl, K.; Sterovsky, T.; Altmann, F.; Steinkellner, H. Expression of functionally active sialylated human erythropoietin in plants. Biotechnol. J., 2013, 8(3), 371-382.
[86]
Castilho, A.; Gruber, C.; Thader, A.; Oostenbrink, C.; Pechlaner, M.; Steinkellner, H.; Altmann, F. Processing of complex N-glycans in IgG Fc-region is affected by core fucosylation. MAbs, 2015, 7(5), 863-870.
[87]
Kamisugi, Y.; Schlink, K.; Rensing, S.A.; Schween, G.; von Stackelberg, M.; Cuming, A.C.; Reski, R.; Cove, D.J. The mechanism of gene targeting in Physcomitrella patens: Homologous recombination, concatenation and multiple integration. Nucleic Acids Res., 2006, 34(21), 6205-6214.
[88]
Reski, R.; Parsons, J.; Decker, E.L. Moss-made pharmaceuticals: From bench to bedside. Plant Biotechnol. J., 2015, 13(8), 1191-1198.
[89]
Huether, C.M.; Lienhart, O.; Baur, A.; Stemmer, C.; Gorr, G.; Reski, R.; Decker, E.L. Glyco-engineering of moss lacking plant-specific sugar residues. Plant Biol (Stuttg), 2005, 7(3), 292-299.
[90]
Patel, D.; Guo, X.; Ng, S.; Melchior, M.; Balderes, P.; Burtrum, D.; Persaud, K.; Luna, X.; Ludwig, D.L.; Kang, X. IgG isotype, glycosylation, and EGFR expression determine the induction of antibody-dependent cellular cytotoxicity in vitro by cetuximab. Hum. Antibodies, 2010, 19(4), 89-99.
[91]
Jarczowski, F.; Kandzia, R.; Thieme, F.; Klimyuk, V.; Gleba, Y. Methods of modulating n-glycosylation site occupancy of plant-produced glycoproteins and recombinant glyco-proteins. US Patent Application, 20160115498, 2016, Aug 28.
[92]
Yusibov, V.; Kushnir, N.; Streatfield, S.J. Antibody Production in plants and green algae. Annu. Rev. Plant Biol., 2016, 67, 669-701.
[93]
Ma, J.K.; Hiatt, A.; Hein, M.; Vine, N.D.; Wang, F.; Stabila, P.; van Dolleweerd, C.; Mostov, K.; Lehner, T. Generation and assembly of secretory antibodies in plants. Science, 1995, 268(5211), 716-719.
[94]
Weintraub, J.A.; Hilton, J.F.; White, J.M.; Hoover, C.I.; Wycoff, K.L.; Yu, L.; Larrick, J.W.; Featherstone, J.D.B. Clinical trial of a plant-derived antibody on recolonization of mutans streptococci. Caries Res., 2005, 39(3), 241-250.
[95]
Ma, J.K-C.; Hikmat, B.Y.; Wycoff, K.; Vine, N.D.; Chargelegue, D.; Yu, L.; Hein, M.B.; Lehner, T. Characterization of a recombinant plant monoclonal secretory antibody and preventive immunotherapy in humans. Nat. Med., 1998, 4(5), 601-606.
[96]
Paul, M.; Ma, J.K-C. Plant-made pharmaceuticals: Leading products and production platforms. Biotechnol. Appl. Biochem., 2011, 58(1), 58-67.
[97]
Vasilev, N.; Smales, C.M.; Schillberg, S.; Fischer, R.; Schiermeyer, A. Developments in the production of mucosal antibodies in plants. Biotechnol. Adv., 2016, 34(2), 77-87.
[98]
Juarez, P.; Virdi, V.; Depicker, A.; Orzaez, D. Biomanufacturing of protective antibodies and other therapeutics in edible plant tissues for oral applications. Plant Biotechnol. J., 2016, 14(9), 1791-1799.
[99]
Juarez, P.; Fernandez-del-Carmen, A.; Rambla, J.L.; Presa, S.; Mico, A.; Granell, A.; Orzaez, D. Evaluation of unintended effects in the composition of tomatoes expressing a human immunoglobulin A against rotavirus. J. Agric. Food Chem., 2014, 62(32), 8158-8168.
[100]
Juarez, P.; Huet-Trujillo, E.; Sarrion-Perdigones, A.; Falconi, E.E.; Granell, A.; Orzaez, D. Combinatorial analysis of secretory immunoglobulin A (sIgA) Expression in Plants. Int. J. Mol. Sci., 2013, 14(3), 6205-6222.
[101]
Virdi, V.; Coddens, A.; De Buck, S.; Millet, S.; Goddeeris, B.M.; Cox, E.; De Greve, H.; Depicker, A. Orally fed seeds producing designer IgAs protect weaned piglets against enterotoxigenic Escherichia coli infection. Proc. Natl. Acad. Sci. USA, 2013, 110(29), 11809-11814.
[102]
Tokuhara, D.; Álvarez, B.; Mejima, M.; Hiroiwa, T.; Takahashi, Y.; Kurokawa, S.; Kuroda, M.; Oyama, M. Ko-zuka-Hata, H.; Nochi, T.; Sagara, H.; Aladin, F.; Marcotte, H.; Frenken, L.G.J.; Iturriza-Gómara, M.; Kiyono, H.; Hammarström, L.; Yuki, Y. Rice-based oral antibody fragment prophylaxis and therapy against rotavirus infection. J. Clin. Invest., 2013, 123, 3829-3838.
[103]
Floss, D.M.; Falkenburg, D.; Conrad, U. Production of vaccines and therapeutic antibodies for veterinary applications in transgenic plants: An overview. Transgenic Res., 2007, 16(3), 315-332.
[104]
Trkola, A.; Purtscher, M.; Muster, T.; Ballaun, C.; Buchacher, A.; Sullivan, N.; Srinivasan, K.; Sodroski, J.; Moore, J.P.; Katinger, H. Human monoclonal antibody 2G12 defines a distinctive neutralization epitope on the gp120 glycoprotein of human immunodeficiency virus type 1. J. Virol., 1996, 70(2), 1100-1108.
[105]
Morris, G.C.; Wiggins, R.C.; Woodhall, S.C.; Bland, J.M.; Taylor, C.R.; Jespers, V.; Vcelar, B.A.; Lacey, C.J. MABGEL 1: First phase 1 trial of the anti-HIV-1 monoclonal antibodies 2F5, 4E10 and 2G12 as a vaginal microbicide. PLoS One, 2014, 9(12), e116153.
[106]
Rademacher, T.; Sack, M.; Arcalis, E.; Stadlmann, J.; Balzer, S.; Altmann, F.; Quendler, H.; Stiegler, G.; Kunert, R.; Fischer, R.; Stoger, E. Recombinant antibody 2G12 produced in maize endosperm efficiently neutralizes HIV-1 and contains predominantly single-GlcNAc N-glycans. Plant Biotechnol. J., 2008, 6(2), 189-201.
[107]
Ma, J.K-C.; Drossard, J.; Lewis, D.; Altmann, F.; Boyle, J.; Christou, P.; Cole, T.; Dale, P.; van Dolleweerd, C.J.; Isitt, V.; Katinger, D.; Lobedan, M.; Mertens, H.; Paul, M.J.; Rademacher, T.; Sack, M.; Hundleby, P.A.C.; Stiegler, G.; Stoger, E.; Twyman, R.M.; Vcelar, B.; Fischer, R. Regulatory approval and a first-in-human phase I clinical trial of a monoclonal antibody produced in transgenic tobacco plants. Plant Biotechnol. J., 2015, 13(8), 1106-1120.
[108]
Paul, M.; Reljic, R.; Klein, K.; Drake, P.M.W.; van Dolleweerd, C.; Pabst, M.; Windwarder, M.; Arcalis, E.; Stoger, E.; Altmann, F.; Cosgrove, C.; Bartolf, A.; Baden, S.; Ma, J.K-C. Characterization of a plant-produced recombinant human secretory IgA with broad neutralizing activity against HIV. MAbs, 2014, 6(6), 1585-1597.
[109]
Gasdaska, J.R.; Sherwood, S.; Regan, J.T.; Dickey, L.F. An afucosylated anti-CD20 monoclonal antibody with greater antibody-dependent cellular cytotoxicity and B-cell depletion and lower complement-dependent cytotoxicity than rituximab. Mol. Immunol., 2012, 50(3), 134-141.
[110]
Grohs, B.M.; Niu, Y.; Veldhuis, L.J.; Trabelsi, S.; Garabagi, F.; Hassell, J.A.; McLean, M.D.; Hall, J.C. Plant-produced trastuzumab inhibits the growth of HER2 positive cancer cells. J. Agric. Food Chem., 2010, 58(18), 10056-10063.
[111]
Hawkins, R.E.; Zhu, D.; Ovecka, M.; Winter, G.; Hamblin, T.J.; Long, A.; Stevenson, F.K. Idiotypic vaccination against human B-cell lymphoma. Rescue of variable region gene sequences from biopsy material for assembly as single-chain Fv personal vaccines. Blood, 1994, 83(11), 3279-3288.
[112]
Hsu, F.J.; Caspar, C.B.; Czerwinski, D.; Kwak, L.W.; Liles, T.M.; Syrengelas, A.; Taidi-Laskowski, B.; Levy, R. Tumor-specific idiotype vaccines in the treatment of patients with B-cell lymphoma--long-term results of a clinical trial. Blood, 1997, 89(9), 3129-3135.
[113]
McCormick, A.A.; Kumagai, M.H.; Hanley, K.; Turpen, T.H.; Hakim, I.; Grill, L.K.; Tusé, D.; Levy, S.; Levy, R. 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, 1999, 96(2), 703-708.
[114]
McCormick, A.A.; Reddy, S.; Reinl, S.J.; Cameron, T.I.; Czerwinkski, D.K.; Vojdani, F.; Hanley, K.M.; Garger, S.J.; White, E.L.; Novak, J.; Barrett, J.; Holtz, R.B.; Tusé, D.; Levy, R. Plant-produced idiotype vaccines for the treatment of non-Hodgkin’s lymphoma: Safety and immunogenicity in a phase I clinical study. Proc. Natl. Acad. Sci. USA, 2008, 105(29), 10131-10136.
[115]
Bendandi, M.; Marillonnet, S.; Kandzia, R.; Thieme, F.; Nickstadt, A.; Herz, S.; Fröde, R.; Inogés, S.; Lòpez-Dìaz de Cerio, A.; Soria, E.; Villanueva, H.; Vancanneyt, G.; McCormick, A.; Tusé, D.; Lenz, J.; Butler-Ransohoff, J-E.; Klimyuk, V.; Gleba, Y. Rapid, high-yield production in plants of individualized idiotype vaccines for non-Hodgkin’s lymphoma. Ann. Oncol., 2010, 21(12), 2420-2427.
[116]
Olinger, G.G., Jr; Pettitt, J.; Kim, D.; Working, C.; Bohorov, O.; Bratcher, B.; Hiatt, E.; Hume, S.D.; Johnson, A.K.; Morton, J.; Pauly, M.; Whaley, K.J.; Lear, C.M.; Biggins, J.E.; Scully, C.; Hensley, L.; Zeitlin, L. Delayed treatment of Ebola virus infection with plant-derived monoclonal antibodies provides protection in rhesus macaques. Proc. Natl. Acad. Sci. USA, 2012, 109(44), 18030-18035.
[117]
Pettitt, J.; Zeitlin, L.; Kim, D.H.; Working, C.; Johnson, J.C.; Bohorov, O.; Bratcher, B.; Hiatt, E.; Hume, S.D.; Johnson, A.K.; Morton, J.; Pauly, M.H.; Whaley, K.J.; Ingram, M.F.; Zovanyi, A.; Heinrich, M.; Piper, A.; Zelko, J.; Olinger, G.G. Therapeutic intervention of Ebola virus infection in rhesus macaques with the MB-003 monoclonal antibody cocktail. Sci. Transl. Med., 2013, 5(199), 199ra113.
[118]
Qiu, X.; Audet, J.; Wong, G.; Fernando, L.; Bello, A.; Pillet, S.; Alimonti, J.B.; Kobinger, G.P. Sustained protection against Ebola virus infection following treatment of infected nonhuman primates with ZMAb. Sci. Rep., 2013, 3, 3365.
[119]
Davey, R.T., Jr; Dodd, L.; Proschan, M.A.; Neaton, J.; Neuhaus Nordwall, J.; Koopmeiners, J.S.; Beigel, J.; Tierney, J.; Lane, H.C.; Fauci, A.S.; Massaquoi, M.B.F.; Sahr, F.; Malvy, D.A. Randomized, Controlled trial of ZMAPP for Ebola virus infection. N. Engl. J. Med., 2016, 375(15), 1448-1456.
[120]
Lyon, G.M.; Mehta, A.K.; Varkey, J.B.; Brantly, K.; Plyler, L.; McElroy, A.K.; Kraft, C.S.; Towner, J.S.; Spiropoulou, C.; Ströher, U.; Uyeki, T.M.; Ribner, B.S. Emory serious communicable diseases unit. Clinical care of two patients with ebola virus disease in the United States. N. Engl. J. Med., 2014, 371, 2402-2409.
[121]
McCarthy, M. US signs contract with ZMapp maker to accelerate development of the Ebola drug. BMJ, 2014, 349, g5488.
[122]
Zeitlin, L.; Bohorov, O.; Bohorova, N.; Hiatt, A.; Kim, D.H.; Pauly, M.H.; Velasco, J.; Whaley, K.J.; Barnard, D.L.; Bates, J.T.; Crowe, J.E., Jr; Piedra, P.A.; Gilbert, B.E. Prophylactic and therapeutic testing of nicotiana-derived RSV-neutralizing human monoclonal antibodies in the cotton rat model. MAbs, 2013, 5(2), 263-269.
[123]
Both, L.; Banyard, A.C.; van Dolleweerd, C.; Horton, D.L.; Ma, J.K-C.; Fooks, A.R. Passive immunity in the prevention of rabies. Lancet Infect. Dis., 2012, 12(5), 397-407.
[124]
Girard, L.S.; Fabis, M.J.; Bastin, M.; Courtois, D.; Pétiard, V.; Koprowski, H. Expression of a human anti-rabies virus monoclonal antibody in tobacco cell culture. Biochem. Biophys. Res. Commun., 2006, 345(2), 602-607.
[125]
Tsekoa, T.L.; Lotter-Stark, T.; Buthelezi, S.; Chakauya, E.; Stoychev, S.H.; Sabeta, C.; Shumba, W.; Phahladira, B.; Hume, S.; Morton, J.; Rupprecht, C.E.; Steinkellner, H.; Pauly, M.; Zeitlin, L.; Whaley, K.; Chikwamba, R. Efficient in vitro and in vivo activity of glyco-engineered plant-produced rabies monoclonal antibodies e559 and 62-71-3. PLoS One, 2016, 11(7), e0159313.
[126]
Azarkar, Z.; Bidaki, M.Z. A case report of inhalation anthrax acquired naturally. BMC Res. Notes, 2016, 9, 141.
[127]
Chen, Z.; Moayeri, M.; Purcell, R. Monoclonal antibody therapies against anthrax. Toxins (Basel), 2011, 3(8), 1004-1019.
[128]
Hull, A.K.; Criscuolo, C.J.; Mett, V.; Groen, H.; Steeman, W.; Westra, H.; Chapman, G.; Legutki, B.; Baillie, L.; Yusibov, V. Human-derived, plant-produced monoclonal antibody for the treatment of anthrax. Vaccine, 2005, 23(17-18), 2082-2086.
[129]
Mett, V.; Chichester, J.A.; Stewart, M.L.; Musiychuk, K.; Bi, H.; Reifsnyder, C.J.; Hull, A.K.; Albrecht, M.T.; Goldman, S.; Baillie, L.W.J.; Yusibov, V. A non-glycosylated, plant-produced human monoclonal antibody against anthrax protective antigen protects mice and non-human primates from B. anthracis spore challenge. Hum. Vaccin., 2011, 7(Suppl.), 183-190.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 26
ISSUE: 3
Year: 2019
Page: [381 - 395]
Pages: 15
DOI: 10.2174/0929867325666171212093257
Price: $58

Article Metrics

PDF: 31
HTML: 2