How Plants Can Contribute to the Supply of Anticancer Compounds

Chapter

Abstract

Plants were the first sources of medicines used by humankind, with evidence of herbal remedies dating back at least 60,000 years. Many plants have been used medicinally because they produce secondary metabolites with pharmacological properties, including compounds such as paclitaxel (Taxol) that inhibit cell division and can therefore be used as a treatment for cancer. With the advent of recombinant DNA and molecular biotechnology in the 1970s, plants have also been modified genetically to produce more of their native pharmaceutically active substances, or even nonnative compounds. The scope of medicinal plants has also expanded beyond secondary metabolites to include pharmaceutical recombinant proteins, such as human antibodies. This chapter provides an overview of the anticancer compounds naturally produced in plants and how gene technology has been used to facilitate their production. It also considers how plant-based expression systems can help to supply modern healthcare systems with protein-based anticancer compounds such as monoclonal antibodies, lectins, and anticancer vaccines.

Keywords

Lectins Monoclonal antibodies Plant molecular pharming Plant secondary metabolites Therapeutic anticancer vaccines 

Abbreviations

ADCC

Antibody-dependent cellular cytotoxicity

ADCs

Antibody-drug conjugates

APIs

Active pharmaceutical ingredients

ATPS

Aqueous two-phase systems

CDC

Complement-dependent cytotoxicity

CHO

Chinese hamster ovary

DoE

Design-of-experiments

EBA

Expanded-bed adsorption

EBV

Epstein-Barr virus

FDA

Food and Drug Administration

GMP

Good manufacturing practice

HBsAg

Hepatitis B-soluble antigen

HBV

Hepatitis B virus

HCPs

Host cell proteins

HPV

Human papillomavirus

mAbs

Monoclonal antibodies

ML1

Mistletoe lectin 1

NK

Natural killer

PAT

Process analytical technology

PEG

Polyethylene glycol

QbD

Quality-by-design

R&D

Research and development

RIP

Ribosome-inactivating protein

RuBisCO

Ribulose-1,5-bisphosphate carboxylase/oxygenase

Th1

T-helper

T-DNA

Transfer DNA

VEGF

Vascular endothelial growth factor

VFUs

Vertical farming units

VLPs

Virus-like particles

Notes

Acknowledgements

The author acknowledges Dr. Richard M Twyman for editorial assistance. This work was funded in part by the European Research Council Advanced Grant “Future-Pharma,” proposal number 269110, and the Fraunhofer-Gesellschaft Internal Programs under Grant No. Attract 125-600164. The author has no conflict of interest to declare.

References

  1. Akagi K, Li J, Broutian TR, Padilla-Nash H, Xiao W, Jiang B, Rocco JW, Teknos TN, Kumar B, Wangsa D, He D, Ried T, Symer DE, Gillison ML (2014) Genome-wide analysis of HPV integration in human cancers reveals recurrent, focal genomic instability. Genome Res 24:185–199PubMedPubMedCentralCrossRefGoogle Scholar
  2. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2002) The molecular basis of cancer-cell behavior. In: Alberts B et al (eds) Molecular biology of the cell, 4th edn. Garland Science, New York, NYGoogle Scholar
  3. Allison N, Richards J (2014) Current status and future trends for disposable technology in the biopharmaceutical industry. J Chem Technol Biotechnol 89:1283–1287CrossRefGoogle Scholar
  4. American Cancer Society (2010) The global economic cost of cancer. American Cancer Society, Atlanta, GAGoogle Scholar
  5. American Cancer Society (2015) Cancer facts and figures 2015. American Cancer Society, Atlanta, GAGoogle Scholar
  6. Angarita M, Muller-Spath T, Baur D, Lievrouw R, Lissens G, Morbidelli M (2015) Twin-column CaptureSMB: a novel cyclic process for protein A affinity chromatography. J Chromatogr A 1389:85–95PubMedCrossRefGoogle Scholar
  7. Arfi ZA, Hellwig S, Drossard J, Fischer R, Buyel JF (2016) Polyclonal antibodies for specific detection of tobacco host cell proteins can be efficiently generated following RuBisCO depletion and the removal of endotoxins. Biotechnol J 11:507–518PubMedCrossRefGoogle Scholar
  8. Asensi M, Ortega A, Mena S, Feddi F, Estrela JM (2011) Natural polyphenols in cancer therapy. Crit Rev Clin Lab Sci 48:197–216PubMedCrossRefGoogle Scholar
  9. Audi J, Belson M, Patel M, Schier J, Osterloh J (2005) Ricin poisoning: a comprehensive review. JAMA 294:2342–2351PubMedCrossRefGoogle Scholar
  10. Aziz A, Aziz S, Li DS, Murphy L, Leone N, Kennedy M, Dhillon S, Van Thiel DH (2006) Efficacy of repeated high-dose hepatitis B vaccine (80 mu g) in patients with chronic liver disease. J Viral Hepat 13:217–221PubMedCrossRefGoogle Scholar
  11. Azzoni AR, Kusnadi AR, Miranda EA, Nikolov ZL (2002) Recombinant aprotinin produced in transgenic corn seed: extraction and purification studies. Biotechnol Bioeng 80:268–276PubMedCrossRefGoogle Scholar
  12. Bachmann MF, Jennings GT (2010) Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns. Nat Rev Immunol 10:787–796PubMedCrossRefGoogle Scholar
  13. Bakker H, Rouwendal GJA, Karnoup AS, Florack DEA, Stoopen GM, Helsper JPFG, Van Ree R, Van Die I, Bosch D (2006) An antibody produced in tobacco expressing a hybrid beta-1,4-galactosyltransferase is essentially devoid of plant carbohydrate epitopes. Proc Natl Acad Sci U S A 103:7577–7582PubMedPubMedCentralCrossRefGoogle Scholar
  14. Baldi A, Bisaria VS, Srivastava AK (2008) Biotechnological approaches for the production of some promising plant-based chemotherapeutics. In: Kayser O, Quax WJ (eds) Medicinal plant biotechnology. Wiley-VCH Verlag GmbH, Hoboken, NJGoogle Scholar
  15. Baldy JL, Elisbao Mdo C, Anzai ET, Pontello R, Reiche EM, Zaha-Inouye MM, Matsuo T, Tonani PC, Ferelle A, Henriques JN, Neves J (2003) Intradermal vaccination of adults with three low doses (2 micrograms) of recombinant hepatitis B vaccine. I. Seroconversion rate and adverse effects. Mem Inst Oswaldo Cruz 98:1101–1107PubMedCrossRefGoogle Scholar
  16. Bals B, Dale BE (2011) Economic comparison of multiple techniques for recovering leaf protein in biomass processing. Biotechnol Bioeng 108:530–537PubMedCrossRefGoogle Scholar
  17. Baneyx F, Mujacic M (2004) Recombinant protein folding and misfolding in Escherichia coli. Nat Biotechnol 22:1399–1408PubMedCrossRefGoogle Scholar
  18. Bang YJ, Van Cutsem E, Feyereislova A, Investigators TT (2010) Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (TOGA): a phase 3, open-label, randomised controlled trial (vol 376, pg 687, 2010). Lancet 376:1302–1302CrossRefGoogle Scholar
  19. 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 13:427–434PubMedCrossRefGoogle Scholar
  20. Baur D, Angarita M, Muller-Spath T, Morbidelli M (2015) Pareto-optimal design of the twin-column CaptureSMB process improves capacity utilization and productivity in protein A affinity capture. Biotechnol J 11:135–145PubMedCrossRefGoogle Scholar
  21. Baxter D (2007) Active and passive immunity, vaccine types, excipients and licensing. Occup Med (Lond) 57:552–556CrossRefGoogle Scholar
  22. Beckman RA, von Roemeling R, Scott AM (2011) Monoclonal antibody dose determination and biodistribution into solid tumors. Ther Deliv 2:333–344PubMedCrossRefGoogle Scholar
  23. Ben-Kasus T, Schechter B, Sela M, Yarden Y (2007) Cancer therapeutic antibodies come of age: targeting minimal residual disease. Mol Oncol 1:42–54PubMedCrossRefGoogle Scholar
  24. Beran J, Ambrozaitis A, Laiskonis A, Mickuviene N, Bacart P, Calozet Y, Demanet E, Heijmans S, Van Belle P, Weber F, Salamand C (2009) Intradermal influenza vaccination of healthy adults using a new microinjection system: a 3-year randomised controlled safety and immunogenicity trial. BMC Med 7:1–15CrossRefGoogle Scholar
  25. Bernstein C, Bernstein H (2015) Epigenetic reduction of DNA repair in progression to gastrointestinal cancer. World J Gastrointest Oncol 7:30–46PubMedPubMedCentralCrossRefGoogle Scholar
  26. Berrington de Gonzalez A, Curtis RE, Kry SF, Gilbert E, Lamart S, Berg CD, Stovall M, Ron E (2011) Proportion of second cancers attributable to radiotherapy treatment in adults: a cohort study in the US SEER cancer registries. Lancet Oncol 12:353–360PubMedCrossRefGoogle Scholar
  27. Bethencourt V (2009) Virus stalls Genzyme plant. Nat Biotechnol 27:681–681CrossRefGoogle Scholar
  28. Bieging KT, Mello SS, Attardi LD (2014) Unravelling mechanisms of p53-mediated tumour suppression. Nat Rev Cancer 14:359–370PubMedPubMedCentralCrossRefGoogle Scholar
  29. Boes A, Spiegel H, Delbruck H, Fischer R, Schillberg S, Sack M (2011) Affinity purification of a framework 1 engineered mouse/human chimeric IgA2 antibody from tobacco. Biotechnol Bioeng 108:2804–2814PubMedCrossRefGoogle Scholar
  30. Bortesi L, Fischer R (2015) The CRISPR/Cas9 system for plant genome editing and beyond. Biotechnol Adv 33:41–52PubMedCrossRefGoogle Scholar
  31. Bosviel R, Dumollard E, Dechelotte P, Bignon YJ, Bernard-Gallon D (2012) Can soy phytoestrogens decrease DNA methylation in BRCA1 and BRCA2 oncosuppressor genes in breast cancer? OMICS 16:235–244PubMedCrossRefGoogle Scholar
  32. Brady G, MacArthur GJ, Farrell PJ (2007) Epstein-Barr virus and Burkitt lymphoma. J Clin Pathol 60:1397–1402PubMedPubMedCentralGoogle Scholar
  33. Buyel JF (2015) Process development strategies in plant molecular farming. Curr Pharm Biotechnol 16:966–982PubMedCrossRefGoogle Scholar
  34. Buyel JF (2016) Procedure to evaluate the efficiency of flocculants for the removal of dispersed particles from plant extracts. J Vis Exp (11):e53940.Google Scholar
  35. Buyel JF, Bautista JA, Fischer R, Yusibov VM (2012) Extraction, purification and characterization of the plant-produced HPV16 subunit vaccine candidate E7 GGG. J Chromatogr B 880:19–26CrossRefGoogle Scholar
  36. Buyel JF, Buyel JJ, Haase C, Fischer R (2015a) The impact of Pseudomonas syringae type III effectors on transient protein expression in tobacco. Plant Biol 17:484–492PubMedCrossRefGoogle Scholar
  37. Buyel JF, Fischer R (2012) Predictive models for transient protein expression in tobacco (Nicotiana tabacum L.) can optimize process time, yield, and downstream costs. Biotechnol Bioeng 109:2575–2588PubMedCrossRefGoogle Scholar
  38. Buyel JF, Fischer R (2013) Processing heterogeneous biomass: overcoming the hurdles in model building. Bioengineered 4:21–24PubMedPubMedCentralCrossRefGoogle Scholar
  39. Buyel JF, Fischer R (2014a) Characterization of complex systems using the design of experiments approach: transient protein expression in tobacco as a case study. J Vis Exp 1:e51216Google Scholar
  40. Buyel JF, Fischer R (2014b) Flocculation increases the efficacy of depth filtration during the downstream processing of recombinant pharmaceutical proteins produced in tobacco. Plant Biotechnol J 12:240–252PubMedCrossRefGoogle Scholar
  41. Buyel JF, Fischer R (2014c) Generic chromatography-based purification strategies accelerate the development of downstream processes for biopharmaceutical proteins produced in plants. Biotechnol J 9:566–577PubMedCrossRefGoogle Scholar
  42. Buyel JF, Fischer R (2014d) A juice extractor can simplify the downstream processing of plant-derived biopharmaceutical proteins compared to blade-based homogenizers. Process Biochem 50:859–866CrossRefGoogle Scholar
  43. Buyel JF, Fischer R (2014e) Scale-down models to optimize a filter train for the downstream purification of recombinant pharmaceutical proteins produced in tobacco leaves. Biotechnol J 9:415–425PubMedCrossRefGoogle Scholar
  44. Buyel JF, Gruchow HM, Boes A, Fischer R (2014a) Rational design of a host cell protein heat precipitation step simplifies the subsequent purification of recombinant proteins from tobacco. Biochem Eng J 88:162–170CrossRefGoogle Scholar
  45. Buyel JF, Gruchow HM, Fischer R (2015b) Depth filters containing diatomite achieve more efficient particle retention than filters solely containing cellulose fibers. Front Plant Sci 6:1–11CrossRefGoogle Scholar
  46. Buyel JF, Gruchow HM, Tödter N, Wehner M (2016a) Determination of the thermal properties of leaves by non-invasive contact free laser probing. J Biotechnol 217:100–108PubMedCrossRefGoogle Scholar
  47. Buyel JF, Hubbuch J and Fischer R (2016b) Comparison of tobacco host cell protein removal methods by blanching intact plants or by heat treatment of extracts. J Vis Exp (9):e54343Google Scholar
  48. Buyel JF, Kaever T, Buyel JJ, Fischer R (2013a) Predictive models for the accumulation of a fluorescent marker protein in tobacco leaves according to the promoter/5′UTR combination. Biotechnol Bioeng 110:471–482PubMedCrossRefGoogle Scholar
  49. Buyel JF, Opdensteinen P, Fischer R (2014b) Cellulose-based filter aids increase the capacity of depth filters during the downstream processing of plant-derived biopharmaceutical proteins. Biotechnol J 10:584–591CrossRefGoogle Scholar
  50. Buyel JF, Twyman RM, Fischer R (2015c) Extraction and downstream processing of plant-derived recombinant proteins. Biotechnol Adv 33:902–913PubMedCrossRefGoogle Scholar
  51. Buyel JF, Twyman RM, Fischer R (2016c) Very-large-scale production of monoclonal antibodies in plants. In: Gottschalk U (ed) Process scale purification of antibodies, 2. Wiley-Interscience, New York, NYGoogle Scholar
  52. Buyel JF, Woo JA, Cramer SM, Fischer R (2013b) The use of quantitative structure-activity relationship models to develop optimized processes for the removal of tobacco host cell proteins during biopharmaceutical production. J Chromatogr A 1322:18–28PubMedCrossRefGoogle Scholar
  53. Camidge R (2001) The story of taxol: nature and politics in the pursuit of an anti-cancer drug. Br Med J 323:115–115CrossRefGoogle Scholar
  54. Caspi RR (2008) Immunotherapy of autoimmunity and cancer: the penalty for success. Nat Rev Immunol 8:970–976PubMedPubMedCentralCrossRefGoogle Scholar
  55. Chabner BA, Roberts TG Jr (2005) Timeline: chemotherapy and the war on cancer. Nat Rev Cancer 5:65–72PubMedCrossRefGoogle Scholar
  56. Chames P, Van Regenmortel M, Weiss E, Baty D (2009) Therapeutic antibodies: successes, limitations and hopes for the future. Br J Pharmacol 157:220–233PubMedPubMedCentralCrossRefGoogle Scholar
  57. Chargelegue D, Vine ND, van Dolleweerd CJ, Drake PMW, Ma JKC (2000) A murine monoclonal antibody produced in transgenic plants with plant-specific glycans is not immunogenic in mice. Transgenic Res 9:187–194PubMedCrossRefGoogle Scholar
  58. Chen H, Chen XZ, Waterboer T, Castro FA, Brenner H (2015) Viral infections and colorectal cancer: a systematic review of epidemiological studies. Int J Cancer 137:12–24PubMedCrossRefGoogle Scholar
  59. Cheson BD, Leonard JP (2008) Monoclonal antibody therapy for B-cell non-Hodgkin’s lymphoma. N Engl J Med 359:613–626PubMedCrossRefGoogle Scholar
  60. Chi RC, Rock MT, Neuzil KM (2010) Immunogenicity and safety of intradermal influenza vaccination in healthy older adults. Clin Infect Dis 50:1331–1338PubMedCrossRefGoogle Scholar
  61. Chial H (2008) Proto-oncogenes to oncogenes to cancer. Nat Educ 1:33Google Scholar
  62. Chiarella P (2011) Production, novel assay development and clinical applications of monoclonal antibodies. Recent Pat Anticancer Drug Discov 6:258–267PubMedCrossRefGoogle Scholar
  63. Christiansen MN, Chik J, Lee L, Anugraham M, Abrahams JL, Packer NH (2014) Cell surface protein glycosylation in cancer. Proteomics 14:525–546PubMedCrossRefGoogle Scholar
  64. Chung C, Christianson M (2014) Predictive and prognostic biomarkers with therapeutic targets in breast, colorectal, and non-small cell lung cancers: a systemic review of current development, evidence, and recommendation. J Oncol Pharm Pract 20:11–28PubMedCrossRefGoogle Scholar
  65. Commandeur U, Twyman RM (2005) Biosafety aspects of molecular farming in plants. In: Fischer R, Schillberg S (eds) Molecular farming. Wiley-VCH Verlag GmbH & Co. KGaA, Hoboken, NJGoogle Scholar
  66. Commandeur U, Twyman RM, Fischer R (2003) The biosafety of molecular farming in plants. AgBiotechNet 5:1–9Google Scholar
  67. Committee for Medicinal Products for Human Use (CHMP) (2004) Erbitux - scientific discussion. European Union, LondonGoogle Scholar
  68. Committee for Medicinal Products for Human Use (CHMP) (2007) Vectibix - scientific discussion. European Union, LondonGoogle Scholar
  69. Committee for Medicinal Products for Human Use (CHMP) (2012) Zaltrap. European Union, LondonGoogle Scholar
  70. Committee for Medicinal Products for Human Use (CHMP) (2015a) Assessment report Abraxane. European Union, LondonGoogle Scholar
  71. Committee for Medicinal Products for Human Use (CHMP) (2015b) Avastin - Annex I: Summary of product characteristics. European Union, LondonGoogle Scholar
  72. Committee for Medicinal Products for Human Use (CHMP) (2015c) Keytruda. European Union, LondonGoogle Scholar
  73. Committee for Medicinal Products for Human Use (CHMP) (2016) Cervarix - Annex I: Summary of product characteristics. European Union, LondonGoogle Scholar
  74. Conley AJ, Joensuu JJ, Jevnikar AM, Menassa R, Brandle JE (2009) Optimization of elastin-like polypeptide fusions for expression and purification of recombinant proteins in plants. Biotechnol Bioeng 103:562–573PubMedCrossRefGoogle Scholar
  75. Conley AJ, Joensuu JJ, Richman A, Menassa R (2011) Protein body-inducing fusions for high-level production and purification of recombinant proteins in plants. Plant Biotechnol J 9:419–433PubMedCrossRefGoogle Scholar
  76. CPMP (2002) Points to consider on quality aspects of medicinal products containing active substances produced by stable transgene expression in higher plants. EMEA, LondonGoogle Scholar
  77. Cummins J, Tangney M (2013) Bacteria and tumours: causative agents or opportunistic inhabitants? Infect Agents Cancer 8:1–8CrossRefGoogle Scholar
  78. Cusido RM, Onrubia M, Sabater-Jara AB, Moyano E, Bonfill M, Goossens A, Angeles Pedreno M, Palazon J (2014) A rational approach to improving the biotechnological production of taxanes in plant cell cultures of Taxus spp. Biotechnol Adv 32:1157–1167PubMedCrossRefGoogle Scholar
  79. D’Este C, de Souza P, Sharman C, Allen S (2012) Relocatable, automated cost-benefit analysis for marine sensor network design. Sensors (Basel) 12:2874–2898CrossRefGoogle Scholar
  80. Das V, Phillips PWB, Khachatourians GG (2008) Commercialization of plant-derived vaccines in Canada: a distant dream? Health Law Rev 16:25–29Google Scholar
  81. De Beer TRM, Bodson C, Dejaegher B, Walczak B, Vercruysse P, Burggraeve A, Lemos A, Delattre L, Heyden YV, Remon JP, Vervaete C, Baeyens WRG (2008) Raman spectroscopy as a process analytical technology (PAT) tool for the in-line monitoring and understanding of a powder blending process. J Pharm Biomed Anal 48:772–779PubMedCrossRefGoogle Scholar
  82. De Vincenzo R, Ricci C, Conte C, Scambia G (2013) HPV vaccine cross-protection: highlights on additional clinical benefit. Gynecol Oncol 130:642–651PubMedCrossRefGoogle Scholar
  83. Distler U, Souady J, Hulsewig M, Drmic-Hofman I, Haier J, Denz A, Grutzmann R, Pilarsky C, Senninger N, Dreisewerd K, Berkenkamp S, Schmidt MA, Peter-Katalinic J, Muthing J (2008) Tumor-associated CD75s- and iso-CD75s-gangliosides are potential targets for adjuvant therapy in pancreatic cancer. Mol Cancer Ther 7:2464–2475PubMedCrossRefGoogle Scholar
  84. Drake PMW, Barbi T, Sexton A, McGowan E, Stadlmann J, Navarre C, Paul MJ, Ma JKC (2009) Development of rhizosecretion as a production system for recombinant proteins from hydroponic cultivated tobacco. FASEB J 23:3581–3589PubMedCrossRefGoogle Scholar
  85. Duffy MJ (2015) Personalized treatment for patients with colorectal cancer: role of biomarkers. Biomark Med 9:337–347PubMedCrossRefGoogle Scholar
  86. Duffy MJ, Lamerz R, Haglund C, Nicolini A, Kalousova M, Holubec L, Sturgeon C (2014) Tumor markers in colorectal cancer, gastric cancer and gastrointestinal stromal cancers: European group on tumor markers 2014 guidelines update. Int J Cancer 134:2513–2522PubMedCrossRefGoogle Scholar
  87. Ecker DM, Jones SD, Levine HL (2015) The therapeutic monoclonal antibody market. MAbs 7:9–14PubMedCrossRefGoogle Scholar
  88. Eiberle MK, Jungbauer A (2010) Technical refolding of proteins: do we have freedom to operate? Biotechnol J 5:547–559PubMedCrossRefGoogle Scholar
  89. Eibl R, Eibl D (2011) Single-use technology in biopharmaceutical manufacture. John Wiley & Sons, Hoboken, NJGoogle Scholar
  90. Eibl R, Kaiser S, Lombriser R, Eibl D (2010) Disposable bioreactors: the current state-of-the-art and recommended applications in biotechnology. Appl Microbiol Biotechnol 86:41–49PubMedCrossRefGoogle Scholar
  91. Endo Y, Tsurugi K, Franz H (1988) The site of action of the A-chain of mistletoe lectin I on eukaryotic ribosomes. The RNA N-glycosidase activity of the protein. FEBS Lett 231:378–380PubMedCrossRefGoogle Scholar
  92. Exposito O, Bonfill M, Moyano E, Onrubia M, Mirjalili MH, Cusido RM, Palazon J (2009) Biotechnological production of taxol and related taxoids: current state and prospects. Anticancer Agents Med Chem 9:109–121PubMedCrossRefGoogle Scholar
  93. Fabricant DS, Farnsworth NR (2001) The value of plants used in traditional medicine for drug discovery. Environ Health Perspect 109:69–75PubMedPubMedCentralCrossRefGoogle Scholar
  94. Faller H, Schuler M, Richard M, Heckl U, Weis J, Kuffner R (2013) Effects of psycho-oncologic interventions on emotional distress and quality of life in adult patients with cancer: systematic review and meta-analysis. J Clin Oncol 31:782–793PubMedCrossRefGoogle Scholar
  95. Farinas CS, Leite A, Miranda EA (2005) Aqueous extraction of recombinant human proinsulin from transgenic maize endosperm. Biotechnol Prog 21:1466–1471PubMedCrossRefGoogle Scholar
  96. FDA (2002) Guidance for Industry: drugs, biologics, and medical devices derived from bioengineered plants for use in humans and animals. Food and Drug Administration, Rockville, MDGoogle Scholar
  97. Fischer R, Schillberg S (2006) Molecular farming: plant-made pharmaceuticals and technical proteins. Wiley-Blackwell, Hoboken, NJGoogle Scholar
  98. Fischer R, Schillberg S, Buyel JF, Twyman RM (2013) Commercial aspects of pharmaceutical protein production in plants. Curr Pharm Des 19:5471–5477PubMedCrossRefGoogle Scholar
  99. Fischer R, Schillberg S, Hellwig S, Twyman RM, Drossard J (2012) GMP issues for recombinant plant-derived pharmaceutical proteins. Biotechnol Adv 30:434–439PubMedCrossRefGoogle Scholar
  100. Fischer R, Vaquero-Martin C, Sack M, Drossard J, Emans N, Commandeur U (1999) Towards molecular farming in the future: transient protein expression in plants. Biotechnol Appl Biochem 30:113–116PubMedGoogle Scholar
  101. Fritz H, Seely D, Kennedy DA, Fernandes R, Cooley K, Fergusson D (2013) Green tea and lung cancer: a systematic review. Integr Cancer Ther 12:7–24PubMedCrossRefGoogle Scholar
  102. Fujita Y (2007) Industrial production of shikonin and berberine. In: Bock G, Marsh J (eds) Ciba Foundation Symposium 137 - applications of plant cell and tissue culture. John Wiley & Sons, Ltd., Hoboken, NJGoogle Scholar
  103. Fuqua JL, Hamorsky K, Khalsa G, Matoba N, Palmer KE (2015) Bulk production of the antiviral lectin griffithsin. Plant Biotechnol J 13:1160–1168PubMedPubMedCentralCrossRefGoogle Scholar
  104. Gabius S, Joshi S, Kayser K, Gabius H (1992) The galactoside-specific lectin from mistletoe as biological response modifier. Int J Oncol 1:705–708PubMedGoogle Scholar
  105. Gajecka M, Rydzanicz M, Jaskula-Sztul R, Wierzbicka M, Szyfter W, Szyfter K (2005) Reduced DNA repair capacity in laryngeal cancer subjects. A comparison of phenotypic and genotypic results. Adv Otorhinolaryngol 62:25–37PubMedGoogle Scholar
  106. Gaughan CL (2015) The present state of the art in expression, production and characterization of monoclonal antibodies. Mol Divers 20:255–270PubMedCrossRefGoogle Scholar
  107. Geli MI, Torrent M, Ludevid D (1994) Two structural domains mediate two sequential events in [gamma]-Zein targeting: protein endoplasmic reticulum retention and protein body formation. Plant Cell 6:1911–1922PubMedPubMedCentralGoogle Scholar
  108. Georgiev MI, Weber J (2014) Bioreactors for plant cells: hardware configuration and internal environment optimization as tools for wider commercialization. Biotechnol Lett 36:1359–1367PubMedCrossRefGoogle Scholar
  109. Gerngross TU (2004) Advances in the production of human therapeutic proteins in yeasts and filamentous fungi. Nat Biotechnol 22:1409–1414PubMedCrossRefGoogle Scholar
  110. Glassman PM, Balthasar JP (2014) Mechanistic considerations for the use of monoclonal antibodies for cancer therapy. Cancer Biol Med 11:20–33PubMedPubMedCentralGoogle Scholar
  111. Gleba YY, Tuse D, Giritch A (2014) Plant viral vectors for delivery by agrobacterium. Curr Top Microbiol Immunol 375:155–192PubMedGoogle Scholar
  112. Glick BR, Pasternak JJ, Patten CL (2010) Molecular biotechnology: principles and applications of recombinant DNA. John Wiley & Sons, Hoboken, NJGoogle Scholar
  113. Gong SJ, Jin CJ, Rha SY, Chung HC (2004) Growth inhibitory effects of trastuzumab and chemotherapeutic drugs in gastric cancer cell lines. Cancer Lett 214:215–224PubMedCrossRefGoogle Scholar
  114. Goody J (1997) Industrial food. Towards the development of a world cuisine. In: Counihan C, van Esterik P (eds) Food and culture. Routledge, LondonGoogle Scholar
  115. Grabowski GA, Golembo M, Shaaltiel Y (2014) Taliglucerase alfa: an enzyme replacement therapy using plant cell expression technology. Mol Genet Metab 112:1–8PubMedCrossRefGoogle Scholar
  116. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70PubMedCrossRefGoogle Scholar
  117. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674PubMedCrossRefGoogle Scholar
  118. Harris LJ, Larson SB, Hasel KW, McPherson A (1997) Refined structure of an intact IgG2a monoclonal antibody. Biochemistry 36:1581–1597PubMedCrossRefGoogle Scholar
  119. Harrison LB, Chadha M, Hill RJ, Hu K, Shasha D (2002) Impact of tumor hypoxia and anemia on radiation therapy outcomes. Oncologist 7:492–508PubMedCrossRefGoogle Scholar
  120. Hassan S, Keshavarz-Moore E, Ma J, Thomas C (2014) Breakage of transgenic tobacco roots for monoclonal antibody release in an ultra-scale down shearing device. Biotechnol Bioeng 111:196–201PubMedCrossRefGoogle Scholar
  121. Hassan S, van Dolleweerd CJ, Ioakeimidis F, Keshavarz-Moore E, Ma JK (2008) Considerations for extraction of monoclonal antibodies targeted to different subcellular compartments in transgenic tobacco plants. Plant Biotechnol J 6:733–748PubMedCrossRefGoogle Scholar
  122. Hellwig S, Drossard J, Twyman RM, Fischer R (2004) Plant cell cultures for the production of recombinant proteins. Nat Biotechnol 22:1415–1422PubMedCrossRefGoogle Scholar
  123. Hernandez J, Mullinax J, Clark W, Toomey P, Villadolid D, Morton C, Ross S, Rosemurgy A (2009) Survival after pancreaticoduodenectomy is not improved by extending resections to achieve negative margins. Ann Surg 250:76–80PubMedCrossRefGoogle Scholar
  124. Heydarnejad MS, Hassanpour DA, Solati DK (2011) Factors affecting quality of life in cancer patients undergoing chemotherapy. Afr Health Sci 11:266–270PubMedPubMedCentralGoogle Scholar
  125. Holland T, Blessing D, Hellwig S, Sack M (2013) The in-line measurement of plant cell biomass using radio frequency impedance spectroscopy as a component of process analytical technology. Biotechnol J 8:1231–1240PubMedGoogle Scholar
  126. Holtz BR, Berquist BR, Bennett LD, Kommineni VJ, Munigunti RK, White EL, Wilkerson DC, Wong KY, Ly LH, Marcel S (2015) Commercial-scale biotherapeutics manufacturing facility for plant-made pharmaceuticals. Plant Biotechnol J 13:1180–1190PubMedCrossRefGoogle Scholar
  127. Hong SN, Lee SM, Kim JH, Lee TY, Kim JH, Choe WH, Lee SY, Cheon YK, Sung IK, Park HS, Shim CS (2012) Helicobacter pylori infection increases the risk of colorectal adenomas: cross-sectional study and meta-analysis. Dig Dis Sci 57:2184–2194PubMedCrossRefGoogle Scholar
  128. Howat S, Park B, Oh IS, Jin YW, Lee EK, Loake GJ (2014) Paclitaxel: biosynthesis, production and future prospects. N Biotechnol 31:242–245PubMedCrossRefGoogle Scholar
  129. Ioannidis JPA (2005) Why most published research findings are false. PLoS Med 2:696–701Google Scholar
  130. Jagadeesh S, Sinha S, Pal BC, Bhattacharya S, Banerjee PP (2007) Mahanine reverses an epigenetically silenced tumor suppressor gene RASSF1A in human prostate cancer cells. Biochem Biophys Res Commun 362:212–217PubMedCrossRefGoogle Scholar
  131. James C (2015) Global status of commercialized biotech/GM Crops: 2015. International Service for the Acquisition of Agri-biotech Applications, Ithaca, NYGoogle Scholar
  132. Jiang QL, Zhang S, Tian M, Zhang SY, Xie T, Chen DY, Chen YJ, He J, Liu J, Ouyang L, Jiang X (2015) Plant lectins, from ancient sugar-binding proteins to emerging anti-cancer drugs in apoptosis and autophagy. Cell Prolif 48:17–28PubMedCrossRefGoogle Scholar
  133. Juca SC, Carvalho PC, Brito FT (2011) A low cost concept for data acquisition systems applied to decentralized renewable energy plants. Sensors (Basel) 11:743–756CrossRefGoogle Scholar
  134. Kapchie VN, Hauck CC, Wang H, Murphy PA (2011) Process improvement for semipurified oleosomes on a pilot-plant scale. J Food Sci 76:C853–C860PubMedCrossRefGoogle Scholar
  135. Kelley B (2007) Very large scale monoclonal antibody purification: the case for conventional unit operations. Biotechnol Prog 23:995–1008PubMedGoogle Scholar
  136. Kelsey RG, Vance NC (1992) Taxol and cephalomannine concentrations in the foliage and bark of shade-grown and sun-exposed taxus brevifolia trees. J Nat Prod 55:912–917CrossRefGoogle Scholar
  137. Kenney RT, Frech SA, Muenz LR, Villar CP, Glenn GM (2004) Dose sparing with intradermal injection of influenza vaccine. N Engl J Med 351:2295–2301PubMedCrossRefGoogle Scholar
  138. Kim TH, Yoo CG, Lamsal BP (2013) Front-end recovery of protein from lignocellulosic biomass and its effects on chemical pretreatment and enzymatic saccharification. Bioprocess Biosyst Eng 36:687–694PubMedCrossRefGoogle Scholar
  139. King-Batoon A, Leszczynska JM, Klein CB (2008) Modulation of gene methylation by genistein or lycopene in breast cancer cells. Environ Mol Mutagen 49:36–45PubMedCrossRefGoogle Scholar
  140. Klutz S, Magnus J, Lobedann M, Schwan P, Maiser B, Niklas J, Temming M, Schembecker G (2015) Developing the biofacility of the future based on continuous processing and single-use technology. J Biotechnol 213:120–130PubMedCrossRefGoogle Scholar
  141. Koprivova A, Stemmer C, Altmann F, Hoffmann A, Kopriva S, Gorr G, Reski R, Decker EL (2004) Targeted knockouts of Physcomitrella lacking plantspecific immunogenic N-glycans. Plant Biotechnol J 2:517–523PubMedCrossRefGoogle Scholar
  142. Kourmanova AG, Soudarkina OJ, Olsnes S, Kozlov JV (2004) Cloning and characterization of the genes encoding toxic lectins in mistletoe (Viscum album L). Eur J Biochem 271:2350–2360PubMedCrossRefGoogle Scholar
  143. Krauspenhaar R, Rypniewski W, Kalkura N, Moore K, DeLucas L, Stoeva S, Mikhailov A, Voelter W, Betzel C (2002) Crystallisation under microgravity of mistletoe lectin I from Viscum album with adenine monophosphate and the crystal structure at 1.9 A resolution. Acta Cryst D Biol Crystallogr 58:1704–1707CrossRefGoogle Scholar
  144. Kubota K (2011) Recent advances and limitations of surgical treatment for pancreatic cancer. World J Clin Oncol 2:225–228PubMedPubMedCentralGoogle Scholar
  145. Kuttan G, Menon LG, Antony S, Kuttan R (1997) Anticarcinogenic and antimetastatic activity of Iscador. Anticancer Drugs 8:15–16CrossRefGoogle Scholar
  146. Kwok R (2011) The real issues in vaccine safety. Nature 473:436–438PubMedCrossRefGoogle Scholar
  147. Kwon SB, Kim MJ, Yang JM, Lee HP, Hong JT, Jeong HS, Kim ES, Yoon DY (2016) Cudrania tricuspidata stem extract induces apoptosis via the extrinsic pathway in SiHa cervical cancer cells. PLoS One 11:e0150235PubMedPubMedCentralCrossRefGoogle Scholar
  148. Landgrebe D, Haake C, Hopfner T, Beutel S, Hitzmann B, Scheper T, Rhiel M, Reardon KF (2010) On-line infrared spectroscopy for bioprocess monitoring. Appl Microbiol Biotechnol 88:11–22PubMedCrossRefGoogle Scholar
  149. Lannoo N, Van Damme EJ (2014) Lectin domains at the frontiers of plant defense. Front Plant Sci 5:397PubMedPubMedCentralGoogle Scholar
  150. Lannoo N, Vervecken W, Proost P, Rouge P, Van Damme EJ (2007) Expression of the nucleocytoplasmic tobacco lectin in the yeast Pichia pastoris. Protein Expr Purif 53:275–282PubMedCrossRefGoogle Scholar
  151. Larsen JS, Curtis WR (2008) Reducing batch-to-batch variability of agrobacterium-mediated transient protein expression in plant tissue culture. AIChE, Philadelphia, PAGoogle Scholar
  152. Laukel M, Rogge P, Dudziak G (2011) Disposable downstream processing for clinical manufacturing. BioProcess Int 9:14–21CrossRefGoogle Scholar
  153. Lee RT, Gabius HJ, Lee YC (1994) The sugar-combining area of the galactose-specific toxic lectin of mistletoe extends beyond the terminal sugar residue: comparison with a homologous toxic lectin, ricin. Carbohydr Res 254:269–276PubMedCrossRefGoogle Scholar
  154. Li CH, Narhi LO, Wen J, Dimitrova M, Wen ZQ, Li J, Pollastrini J, Nguyen X, Tsuruda T, Jiang YJ (2012) Effect of pH, temperature, and salt on the stability of Escherichia coli- and Chinese hamster ovary cell-derived IgG1 Fc. Biochemistry 51:10056–10065PubMedCrossRefGoogle Scholar
  155. Li F, Vijayasankaran N, Shen A, Kiss R, Amanullah A (2010) Cell culture processes for monoclonal antibody production. MAbs 2:466–479PubMedPubMedCentralCrossRefGoogle Scholar
  156. Li YF (2011) Self-cleaving fusion tags for recombinant protein production. Biotechnol Lett 33:869–881PubMedCrossRefGoogle Scholar
  157. Lightfoot EN, Moscariello JS (2004) Bioseparations. Biotechnol Bioeng 87:259–273PubMedCrossRefGoogle Scholar
  158. Lightfoot EN, Root TW, O’Dell JL (2008) Emergence of ideal membrane cascades for downstream processing. Biotechnol Prog 24:599–605PubMedCrossRefGoogle Scholar
  159. Linden W, Girgis A (2012) Psychological treatment outcomes for cancer patients: what do meta-analyses tell us about distress reduction? Psychooncology 21:343–350PubMedCrossRefGoogle Scholar
  160. Lolas A (2013) Microbial control strategies in bioprocessing falling short of assuring product quality and satisfying regulatory expectations. CompareNetworks, Fishers, INGoogle Scholar
  161. Lorence A, Verpoorte R (2004) Gene transfer and expression in plants. Methods Mol Biol 267:329–350PubMedGoogle Scholar
  162. Ma JK, Chikwamba R, Sparrow P, Fischer R, Mahoney R, Twyman RM (2005) Plant-derived pharmaceuticals--the road forward. Trends Plant Sci 10:580–585PubMedCrossRefGoogle Scholar
  163. Ma JK, Drossard J, Lewis D, Altmann F, Boyle J, Christou P, Cole T, Dale P, van Dolleweerd CJ, Isitt V, Katinger D, Lobedan M, Mertens H, Paul MJ, Rademacher T, Sack M, Hundleby PA, Stiegler G, Stoger E, Twyman RM, Vcelar B, Fischer R (2015) Regulatory approval and a first-in-human phase I clinical trial of a monoclonal antibody produced in transgenic tobacco plants. Plant Biotechnol J 13:1106–1120PubMedCrossRefGoogle Scholar
  164. Manegold C (2014) Treatment algorithm in 2014 for advanced non-small cell lung cancer: therapy selection by tumour histology and molecular biology. Adv Med Sci 59:308–313PubMedCrossRefGoogle Scholar
  165. Markley N, Nykiforuk C, Boothe J, Moloney M (2006) Producing proteins using transgenic oilbody-oleosin technology. BioPharm Int 19:34–57Google Scholar
  166. Massa S, Franconi R, Brandi R, Muller A, Mett V, Yusibov V, Venuti A (2007) Anti-cancer activity of plant-produced HPV16 E7 vaccine. Vaccine 25:3018–3021PubMedCrossRefGoogle Scholar
  167. Mauch P, Constine L, Greenberger J, Knospe W, Sullivan J, Liesveld JL, Deeg HJ (1995) Hematopoietic stem cell compartment: acute and late effects of radiation therapy and chemotherapy. Int J Radiat Oncol Biol Phys 31:1319–1339PubMedCrossRefGoogle Scholar
  168. McAllister SD, Soroceanu L, Desprez PY (2015) The antitumor activity of plant-derived non-psychoactive cannabinoids. J Neuroimmune Pharmacol 10:255–267PubMedPubMedCentralCrossRefGoogle Scholar
  169. McCormack PL (2014) Quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine (Gardasil((R))): a review of its use in the prevention of premalignant anogenital lesions, cervical and anal cancers, and genital warts. Drugs 74:1253–1283PubMedCrossRefGoogle Scholar
  170. 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 U S A 96:703–708PubMedPubMedCentralCrossRefGoogle Scholar
  171. McGuire S (2016) World cancer report 2014. Geneva, Switzerland: World Health Organization, International Agency for Research on Cancer, WHO Press, 2015. Adv Nutr 7:418–419PubMedPubMedCentralCrossRefGoogle Scholar
  172. McLean MD, Chen RJ, Yu DQ, Mah KZ, Teat J, Wang HF, Zaplachinski S, Boothe J, Hall JC (2012) Purification of the therapeutic antibody trastuzumab from genetically modified plants using safflower Protein A-oleosin oilbody technology. Transgenic Res 21:1291–1301PubMedCrossRefGoogle Scholar
  173. Mellstedt H (2003) Monoclonal antibodies in human cancer. Drugs Today (Barc) 39:1–16Google Scholar
  174. Menkhaus TJ, Bai Y, Zhang C, Nikolov ZL, Glatz CE (2004) Considerations for the recovery of recombinant proteins from plants. Biotechnol Prog 20:1001–1014PubMedCrossRefGoogle Scholar
  175. Menkhaus TJ, Glatz CE (2005) Antibody capture from corn endosperm extracts by packed bed and expanded bed adsorption. Biotechnol Prog 21:473–485PubMedCrossRefGoogle Scholar
  176. Menkhaus TJ, Roseland J (2008) Recovery of proteins from corn and soybean extracts by membrane adsorption. Biotechnol Prog 24:1075–1084PubMedCrossRefGoogle Scholar
  177. Menzel S, Holland T, Boes A, Spiegel H, Bolzenius J, Fischer R, Buyel JF (2016) Optimized blanching reduces the host cell protein content and substantially enhances the recovery and stability of two plant-derived malaria vaccine candidates. Front Plant Sci 7:1–15CrossRefGoogle Scholar
  178. Merrett ND (2014) Multimodality treatment of potentially curative gastric cancer: geographical variations and future prospects. World J Gastroenterol 20:12892–12899PubMedPubMedCentralCrossRefGoogle Scholar
  179. Millner LM, Strotman LN (2016) The future of precision medicine in oncology. Clin Lab Med 36:557–573PubMedCrossRefGoogle Scholar
  180. Minchinton AI, Tannock IF (2006) Drug penetration in solid tumours. Nat Rev Cancer 6:583–592PubMedCrossRefGoogle Scholar
  181. Mor TS (2015) Molecular pharming’s foot in the FDA’s door: protalix’s trailblazing story. Biotechnol Lett 37:2147–2150PubMedPubMedCentralCrossRefGoogle Scholar
  182. Mukherjee AK, Basu S, Sarkar N, Ghosh AC (2001) Advances in cancer therapy with plant based natural products. Curr Med Chem 8:1467–1486PubMedCrossRefGoogle Scholar
  183. Murphy KP, Travers P, Walport M, Janeway C (2008) Janeway’s immunobiology. Garland Science, New York, NYGoogle Scholar
  184. Muthing J, Meisen I, Bulau P, Langer M, Witthohn K, Lentzen H, Neumann U, Peter-Katalinic J (2004) Mistletoe lectin I is a sialic acid-specific lectin with strict preference to gangliosides and glycoproteins with terminal Neu5Ac alpha 2-6Gal beta 1-4GlcNAc residues. Biochemistry 43:2996–3007PubMedCrossRefGoogle Scholar
  185. Napier JA, Stobart AK, Shewry PR (1996) The structure and biogenesis of plant oil bodies: the role of the ER membrane and the oleosin class of proteins. Plant Mol Biol 31:945–956PubMedCrossRefGoogle Scholar
  186. Nardin EH, Oliveira GA, Calvo-Calle JM, Wetzel K, Maier C, Birkett AJ, Sarpotdar P, Corado ML, Thornton GB, Schmidt A (2004) Phase I testing of a malaria vaccine composed of hepatitis B virus core particles expressing Plasmodium falciparum circumsporozoite epitopes. Infect Immun 72:6519–6527PubMedPubMedCentralCrossRefGoogle Scholar
  187. Neidle S, Thurston DE (2005) Chemical approaches to the discovery and development of cancer therapies. Nat Rev Cancer 5:285–296PubMedCrossRefGoogle Scholar
  188. Newell CA (2000) Plant transformation technology - developments and applications. Mol Biotechnol 16:53–65PubMedCrossRefGoogle Scholar
  189. Nfor BK, Zuluaga DS, Verheijen PJT, Verhaert PDEM, van der Wielen LAM, Ottens M (2011) Model-based rational strategy for chromatographic resin selection. Biotechnol Prog 27:1629–1643PubMedCrossRefGoogle Scholar
  190. Niwa H, Tonevitsky AG, Agapov II, Saward S, Pfuller U, Palmer RA (2003) Crystal structure at 3 A of mistletoe lectin I, a dimeric type-II ribosome-inactivating protein, complexed with galactose. Eur J Biochem 270:2739–2749PubMedCrossRefGoogle Scholar
  191. Nuzzo R (2014) Scientific method: statistical errors. Nature 506:150–152PubMedCrossRefGoogle Scholar
  192. O’Brien TP, Brown LA, Battersby DG, Rudolph AS, Raman LP (2012) Large-scale, single-use depth filtration systems for mammalian cell culture clarification. BioProcess Int 10:50–57Google Scholar
  193. O’Keefe BR, Vojdani F, Buffa V, Shattock RJ, Montefiori DC, Bakke J, Mirsalis J, d’Andrea AL, Hume SD, Bratcher B, Saucedo CJ, McMahon JB, Pogue GP, Palmer KE (2009) Scaleable manufacture of HIV-1 entry inhibitor griffithsin and validation of its safety and efficacy as a topical microbicide component. Proc Natl Acad Sci U S A 106:6099–6104PubMedPubMedCentralCrossRefGoogle Scholar
  194. O’Neill KM, Larsen JS, Curtis WR (2008) Scale-up of Agrobacterium-mediated transient protein expression in bioreactor-grown Nicotiana glutinosa plant cell suspension culture. Biotechnol Prog 24:372–376PubMedCrossRefGoogle Scholar
  195. Oliveira C, Felix W, Moreira RA, Teixeira JA, Domingues L (2008) Expression of frutalin, an alpha-D-galactose-binding jacalin-related lectin, in the yeast Pichia pastoris. Protein Expr Purif 60:188–193PubMedCrossRefGoogle Scholar
  196. Olsnes S, Stirpe F, Sandvig K, Pihl A (1982) Isolation and characterization of viscumin, a toxic lectin from Viscum album L. (mistletoe). J Biol Chem 257:13263–13270PubMedGoogle Scholar
  197. Orr V, Zhong LY, Moo-Young M, Chou CP (2013) Recent advances in bioprocessing application of membrane chromatography. Biotechnol Adv 31:450–465PubMedCrossRefGoogle Scholar
  198. Ouattara A, Laurens MB (2015) Vaccines against malaria. Clin Infect Dis 60:930–936PubMedCrossRefGoogle Scholar
  199. Pastores GM, Petakov M, Giraldo P, Rosenbaum H, Szer J, Deegan PB, Amato DJ, Mengel E, Tan ES, Chertkoff R, Brill-Almon E, Zimran A (2014) A Phase 3, multicenter, open-label, switchover trial to assess the safety and efficacy of taliglucerase alfa, a plant cell-expressed recombinant human glucocerebrosidase, in adult and pediatric patients with Gaucher disease previously treated with imiglucerase. Blood Cells Mol Dis 53:253–260PubMedCrossRefGoogle Scholar
  200. Paul M, Ma JK (2011) Plant-made pharmaceuticals: leading products and production platforms. Biotechnol Appl Biochem 58:58–67PubMedCrossRefGoogle Scholar
  201. Paul MJ, Teh AYH, Twyman RM, Ma JKC (2013) Target product selection - where can molecular pharming make the difference? Curr Pharm Des 19:5478–5485PubMedCrossRefGoogle Scholar
  202. Pereira DM, Valentao P, Correia-da-Silva G, Teixeira N, Andrade PB (2012) Plant secondary metabolites in cancer chemotherapy: where are we? Curr Pharm Biotechnol 13:632–650PubMedCrossRefGoogle Scholar
  203. Peters C, Brown S (2015) Antibody-drug conjugates as novel anti-cancer chemotherapeutics. Biosci Rep 35:1–20CrossRefGoogle Scholar
  204. PhRMA (2014) Pharmaceutical Industry Profile - PhRMA annual membership survey. Pharmaceutical Research and Manufacturers of America, Washington, DCGoogle Scholar
  205. Polakis P (2016) Antibody drug conjugates for cancer therapy. Pharmacol Rev 68:3–19PubMedCrossRefGoogle Scholar
  206. Polireddy K, Chen Q (2016) Cancer of the pancreas: molecular pathways and current advancement in treatment. J Cancer 7:1497–1514PubMedPubMedCentralCrossRefGoogle Scholar
  207. Poljak M (2012) Prophylactic human papillomavirus vaccination and primary prevention of cervical cancer: issues and challenges. Clin Microbiol Infect 18:64–69PubMedCrossRefGoogle Scholar
  208. Pritzkuleit R, Beske F, Katalinic A (2010) Demographic change and cancer. Onkologie 33:19–24PubMedCrossRefGoogle Scholar
  209. Puchta H, Fauser F (2014) Synthetic nucleases for genome engineering in plants: prospects for a bright future. Plant J 78:727–741PubMedCrossRefGoogle Scholar
  210. Raees MA, Hussain H, Al-Rawahi A, Csuk R, Muhammad SA, Khan HY, Rehman NU, Abbas G, Al-Broumi MA, Green IR, Elyassi A, Mahmood T, Al-Harrasi A (2016) Anti-proliferative and computational studies of two new pregnane glycosides from Desmidorchis flava. Bioorg Chem 67:95–104PubMedCrossRefGoogle Scholar
  211. Rathore AS (2009) Roadmap for implementation of quality by design (QbD) for biotechnology products. Trends Biotechnol 27:546–553PubMedCrossRefGoogle Scholar
  212. Rathore AS, Bhambure R, Ghare V (2010) Process analytical technology (PAT) for biopharmaceutical products. Anal Bioanal Chem 398:137–154PubMedCrossRefGoogle Scholar
  213. Rathore AS, Yu M, Yeboah S, Sharma A (2008) Case study and application of process analytical technology (PAT) towards bioprocessing: use of on-line high-performance liquid chromatography (HPLC) for making real-time pooling decisions for process chromatography. Biotechnol Bioeng 100:306–316PubMedCrossRefGoogle Scholar
  214. Read EK, Park JT, Shah RB, Riley BS, Brorson KA, Rathore AS (2010a) Process analytical technology (PAT) for biopharmaceutical products: Part I. Concepts and applications. Biotechnol Bioeng 105:276–284PubMedCrossRefGoogle Scholar
  215. Read EK, Shah RB, Riley BS, Park JT, Brorson KA, Rathore AS (2010b) Process analytical technology (PAT) for biopharmaceutical products: Part II. Concepts and applications. Biotechnol Bioeng 105:285–295PubMedCrossRefGoogle Scholar
  216. Research B (2013) Biologic therapeutic drugs: technologies and global markets. BCC Research LLC, Wellesley, MAGoogle Scholar
  217. Reuter LJ, Bailey MJ, Joensuu JJ, Ritala A (2014) Scale-up of hydrophobin-assisted recombinant protein production in tobacco BY-2 suspension cells. Plant Biotechnol J 12:402–410PubMedCrossRefGoogle Scholar
  218. Rivera AL, Gomez-Lim M, Fernandez F, Loske AM (2012) Physical methods for genetic plant transformation. Phys Life Rev 9:308–345PubMedCrossRefGoogle Scholar
  219. Rosenberg Y, Sack M, Montefiori D, Forthal D, Mao LJ, Hernandez-Abanto S, Urban L, Landucci G, Fischer R, Jiang XM (2013) Rapid high-level production of functional HIV broadly neutralizing monoclonal antibodies in transient plant expression systems. PLoS One 8:e58724PubMedPubMedCentralCrossRefGoogle Scholar
  220. Rottenberg Y, Barchana M, Liphshitz I, Peretz T (2010) The changing face of cancer in the elderly: only a demographic change? Arch Gerontol Geriatr 50:e59–e62PubMedCrossRefGoogle Scholar
  221. Sainz B, Antolin J, Lopez-Coronado M, de Castro C (2013) A novel low-cost sensor prototype for monitoring temperature during wine fermentation in tanks. Sensors (Basel) 13:2848–2861CrossRefGoogle Scholar
  222. Salama JK, Chmura SJ (2014) The role of surgery and ablative radiotherapy in oligometastatic breast cancer. Semin Oncol 41:790–797PubMedCrossRefGoogle Scholar
  223. Sankaranarayanan R (2014) Screening for cancer in low- and middle-income countries. Ann Glob Health 80:412–417PubMedCrossRefGoogle Scholar
  224. Santos RB, Abranches R, Fischer R, Sack M, Holland T (2016) Putting the spotlight back on plant suspension cultures. Front Plant Sci 7:297PubMedPubMedCentralCrossRefGoogle Scholar
  225. Schillberg S, Raven N, Fischer R, Twyman RM, Schiermeyer A (2013) Molecular farming of pharmaceutical proteins using plant suspension cell and tissue cultures. Curr Pharm Des 19:5531–5542PubMedCrossRefGoogle Scholar
  226. Schilsky RL (2010) Personalized medicine in oncology: the future is now. Nat Rev Drug Discov 9:363–366PubMedCrossRefGoogle Scholar
  227. Schnekenburger M, Dicato M, Diederich M (2014) Plant-derived epigenetic modulators for cancer treatment and prevention. Biotechnol Adv 32:1123–1132PubMedCrossRefGoogle Scholar
  228. Schork NJ (2015) Personalized medicine: time for one-person trials. Nature 520:609–611PubMedCrossRefGoogle Scholar
  229. Schuster M, Nechansky A, Kircheis R (2006) Cancer immunotherapy. Biotechnol J 1:138–147PubMedCrossRefGoogle Scholar
  230. Scott AM, Wolchok JD, Old LJ (2012) Antibody therapy of cancer. Nat Rev Cancer 12:278–287PubMedCrossRefGoogle Scholar
  231. Scotti N, Rybicki EP (2013) Virus-like particles produced in plants as potential vaccines. Expert Rev Vaccines 12:211–224PubMedCrossRefGoogle Scholar
  232. Selvi BR, Pradhan SK, Shandilya J, Das C, Sailaja BS, Shankar GN, Gadad SS, Reddy A, Dasgupta D, Kundu TK (2009) Sanguinarine interacts with chromatin, modulates epigenetic modifications, and transcription in the context of chromatin. Chem Biol 16:203–216CrossRefGoogle Scholar
  233. Senter PD (2009) Potent antibody drug conjugates for cancer therapy. Curr Opin Chem Biol 13:235–244PubMedCrossRefGoogle Scholar
  234. Sfikakis PP, Gourgoulis GM, Moulopoulos LA, Kouvatseas G, Theofilopoulos AN, Dimopoulos MA (2005) Age-related thymic activity in adults following chemotherapy-induced lymphopenia. Eur J Clin Invest 35:380–387PubMedCrossRefGoogle Scholar
  235. Shahid S (2016) Review of hematological indices of cancer patients receiving combined chemotherapy & radiotherapy or receiving radiotherapy alone. Crit Rev Oncol/Hematol 105:145–155CrossRefGoogle Scholar
  236. Shoji Y, Farrance CE, Bautista J, Bi H, Musiychuk K, Horsey A, Park H, Jaje J, Green BJ, Shamloul M, Sharma S, Chichester JA, Mett V, Yusibov V (2012) A plant-based system for rapid production of influenza vaccine antigens. Influenza Other Respi Viruses 6:204–210CrossRefGoogle Scholar
  237. Shukla AA, Gottschalk U (2013) Single-use disposable technologies for biopharmaceutical manufacturing. Trends Biotechnol 31:147–154PubMedCrossRefGoogle Scholar
  238. Shukla AA, Thommes J (2010) Recent advances in large-scale production of monoclonal antibodies and related proteins. Trends Biotechnol 28:253–261PubMedCrossRefGoogle Scholar
  239. Siddiqui M, Rajkumar SV (2012) The high cost of cancer drugs and what we can do about it. Mayo Clin Proc 87:935–943PubMedPubMedCentralCrossRefGoogle Scholar
  240. Silverstein A, Silverstein VB, Nunn LS (2006) Cancer: conquering a deadly disease. Twenty-first century books, Minneapolis, MNGoogle Scholar
  241. Small E, Catling PM (1999) Canadian medicinal crops. NRC Research Press, Ottawa, ONGoogle Scholar
  242. Sonnenschein C, Soto AM (2013) The aging of the 2000 and 2011 Hallmarks of cancer reviews: a critique. J Biosci 38:651–663PubMedPubMedCentralCrossRefGoogle Scholar
  243. Souza MA, Carvalho FC, Ruas LP, Ricci-Azevedo R, Roque-Barreira MC (2013) The immunomodulatory effect of plant lectins: a review with emphasis on ArtinM properties. Glycoconj J 30:641–657PubMedPubMedCentralCrossRefGoogle Scholar
  244. Sparrow PAC, Irwin JA, Dale PJ, Twyman RM, Ma JKC (2007) Pharma-planta: road testing the developing regulatory guidelines for plant-made pharmaceuticals. Transgenic Res 16:147–161PubMedCrossRefGoogle Scholar
  245. Spiegel H, Boes A, Voepel N, Beiss V, Edgue G, Rademacher T, Sack M, Schillberg S, Reimann A, Fischer R (2015) Application of a scalable plant transient gene expression platform for malaria vaccine development. Front Plant Sci 6:1169PubMedPubMedCentralCrossRefGoogle Scholar
  246. Spiegel H, Stöger E, Twyman RM, Buyel JF (2016) Current status and perspectives of the molecular farming landscape. In: Kermode AR (ed) Molecular pharming: applications, challenges and emerging areas. Wiley-VCH, WeinheimGoogle Scholar
  247. Spok A (2007) Molecular farming on the rise--GMO regulators still walking a tightrope. Trends Biotechnol 25:74–82PubMedCrossRefGoogle Scholar
  248. Stoger E, Fischer R, Moloney M, Ma JKC (2014) Plant molecular pharming for the treatment of chronic and infectious diseases. Annu Rev Plant Biol 65:743–768PubMedCrossRefGoogle Scholar
  249. 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 Breed 9:149–158CrossRefGoogle Scholar
  250. Strasser R (2013) Engineering of human-type O-glycosylation in Nicotiana benthamiana plants. Bioengineered 4:191–196PubMedCrossRefGoogle Scholar
  251. Strasser R (2016) Plant protein glycosylation. Glycobiology 26(9):926–939PubMedPubMedCentralCrossRefGoogle Scholar
  252. Strasser R, Stadlmann J, Schahs M, Stiegler G, Quendler H, Mach L, Glossl 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 6:392–402PubMedCrossRefGoogle Scholar
  253. Sudhakar A (2009) History of cancer, ancient and modern treatment methods. J Cancer Sci Ther 1:1–4PubMedPubMedCentralCrossRefGoogle Scholar
  254. Tabata H (2004) Paclitaxel production by plant-cell-culture technology. Adv Biochem Eng Biotechnol 87:1–23PubMedGoogle Scholar
  255. The CMC Biotech Working Group (2009) A-Mab: a case study in bioprocess development. CASSS - An International Separation Science Society, Emeryville, CAGoogle Scholar
  256. Thierry-Carstensen B, Dalby T, Stevner MA, Robbins JB, Schneerson R, Trollfors B (2013) Experience with monocomponent acellular pertussis combination vaccines for infants, children, adolescents and adults-A review of safety, immunogenicity, efficacy and effectiveness studies and 15 years of field experience. Vaccine 31:5178–5191PubMedCrossRefGoogle Scholar
  257. Tian L, Sun SSM (2011) A cost-effective ELP-intein coupling system for recombinant protein purification from plant production platform. PLoS One 6:e24183PubMedPubMedCentralCrossRefGoogle Scholar
  258. Torrent M, Llompart B, Lasserre-Ramassamy S, Llop-Tous I, Bastida M, Marzabal P, Westerholm-Parvinen A, Saloheimo M, Heifetz PB, Ludevid MD (2009) Eukaryotic protein production in designed storage organelles. BMC Biol 7:5PubMedPubMedCentralCrossRefGoogle Scholar
  259. Tremblay R, Diao H, Huner N, Jevnikar AM, Ma SW (2011) The development, characterization, and demonstration of a novel strategy for purification of recombinant proteins expressed in plants. Transgenic Res 20:1357–1366PubMedCrossRefGoogle Scholar
  260. Trueb RM (2010) Chemotherapy-induced hair loss. Skin Therapy Lett 15:5–7PubMedGoogle Scholar
  261. Twyman RM, Stoger E, Schillberg S, Christou P, Fischer R (2003) Molecular farming in plants: host systems and expression technology. Trends Biotechnol 21:570–578PubMedCrossRefGoogle Scholar
  262. UniProt-Consortium (2012) Reorganizing the protein space at the Universal Protein Resource (UniProt). Nucleic Acids Res 40:D71–D75CrossRefGoogle Scholar
  263. Urry D (1988) Entropic elastic processes in protein mechanisms. I. Elastic structure due to an inverse temperature transition and elasticity due to internal chain dynamics. J Protein Chem 7:1–34PubMedCrossRefGoogle Scholar
  264. Valentine L (2003) Agrobacterium tumefaciens and the plant: the David and Goliath of modern genetics. Plant Physiol 133:948–955PubMedPubMedCentralCrossRefGoogle Scholar
  265. Van Damme EJ (2014) History of plant lectin research. Methods Mol Biol 1200:3–13PubMedCrossRefGoogle Scholar
  266. Vandenborre G, Smagghe G, Van Damme EJ (2011) Plant lectins as defense proteins against phytophagous insects. Phytochemistry 72:1538–1550PubMedCrossRefGoogle Scholar
  267. Venuti A, Massa S, Mett V, Vedova LD, Paolini F, Franconi R, Yusibov V (2009) An E7-based therapeutic vaccine protects mice against HPV16 associated cancer. Vaccine 27:3395–3397PubMedCrossRefGoogle Scholar
  268. Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN, Harris M, Reni M, Dowden S, Laheru D, Bahary N, Ramanathan RK, Tabernero J, Hidalgo M, Goldstein D, Van Cutsem E, Wei X, Iglesias J, Renschler MF (2013) Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 369:1691–1703PubMedPubMedCentralCrossRefGoogle Scholar
  269. Wahl O, Oswald M, Tretzel L, Herres E, Arend J, Efferth T (2011) Inhibition of tumor angiogenesis by antibodies, synthetic small molecules and natural products. Curr Med Chem 18:3136–3155PubMedCrossRefGoogle Scholar
  270. Walsh MJ, Dodd JE, Hautbergue GM (2013) Ribosome-inactivating proteins: potent poisons and molecular tools. Virulence 4:774–784PubMedPubMedCentralCrossRefGoogle Scholar
  271. Wang JW, Roden RBS (2013) Virus-like particles for the prevention of human papillomavirus-associated malignancies. Expert Rev Vaccines 12:129–141PubMedCrossRefGoogle Scholar
  272. Wani MC, Horwitz SB (2014) Nature as a remarkable chemist: a personal story of the discovery and development of Taxol. Anticancer Drugs 25:482–487PubMedPubMedCentralCrossRefGoogle Scholar
  273. Weinberg RA (2006) The biology of cancer. Garland Science, Milton ParkGoogle Scholar
  274. Weiner LM, Murray JC, Shuptrine CW (2012) Antibody-based immunotherapy of cancer. Cell 148:1081–1084PubMedPubMedCentralCrossRefGoogle Scholar
  275. Whitford WG (2010) Single-use systems as principal components in bioproduction. BioProcess Int 8:34–44Google Scholar
  276. Wilken LR, Nikolov ZL (2012) Recovery and purification of plant-made recombinant proteins. Biotechnol Adv 30:419–433PubMedCrossRefGoogle Scholar
  277. Wilson SA, Roberts SC (2012) Recent advances towards development and commercialization of plant cell culture processes for the synthesis of biomolecules. Plant Biotechnol J 10:249–268PubMedCrossRefGoogle Scholar
  278. Winkelnkemper T, Schembecker G (2010) Purification performance index and separation cost indicator for experimentally based systematic downstream process development. Sep Purif Technol 72:34–39CrossRefGoogle Scholar
  279. Wirz H, Sauer-Budge AF, Briggs J, Sharpe A, Shu SD, Sharon A (2012) Automated production of plant-based vaccines and pharmaceuticals. J Lab Autom 17:449–457PubMedCrossRefGoogle Scholar
  280. Wurm FM (2004) Production of recombinant protein therapeutics in cultivated mammalian cells. Nat Biotechnol 22:1393–1398PubMedCrossRefGoogle Scholar
  281. Yabroff KR, Lund J, Kepka D, Mariotto A (2011) Economic burden of cancer in the United States: estimates, projections, and future research. Cancer Epidemiol Biomarkers Prev 20:2006–2014PubMedPubMedCentralCrossRefGoogle Scholar
  282. Zarkovic N, Kalisnik T, Loncaric I, Borovic S, Mang S, Kissel D, Konitzer M, Jurin M, Grainza S (1998) Comparison of the effects of Viscum album lectin ML-1 and fresh plant extract (Isorel) on the cell growth in vitro and tumorigenicity of melanoma B16F10. Cancer Biother Radiopharm 13:121–131PubMedCrossRefGoogle Scholar
  283. Zhong JJ (2002) Plant cell culture for production of paclitaxel and other taxanes. J Biosci Bioeng 94:591–599PubMedCrossRefGoogle Scholar
  284. Zimran A, Brill-Almon E, Chertkoff R, Petakov M, Blanco-Favela F, Munoz ET, Solorio-Meza SE, Amato D, Duran G, Giona F, Heitner R, Rosenbaum H, Giraldo P, Mehta A, Park G, Phillips M, Elstein D, Altarescu G, Szleifer M, Hashmueli S, Aviezer D (2011) Pivotal trial with plant cell-expressed recombinant glucocerebrosidase, taliglucerase alfa, a novel enzyme replacement therapy for Gaucher disease. Blood 118:5767–5773PubMedCrossRefGoogle Scholar
  285. Zischewski J, Sack M, Fischer R (2015) Overcoming low yields of plant-made antibodies by a protein engineering approach. Biotechnol J 11:107–116PubMedCrossRefGoogle Scholar
  286. Zlotogorski A, Dayan A, Dayan D, Chaushu G, Salo T, Vered M (2013) Nutraceuticals as new treatment approaches for oral cancer: II. Green tea extracts and resveratrol. Oral Oncol 49:502–506PubMedCrossRefGoogle Scholar
  287. Zwierzina H, Bergmann L, Fiebig H, Aamdal S, Schoffski P, Witthohn K, Lentzen H (2011) The preclinical and clinical activity of aviscumine: a potential anticancer drug. Eur J Cancer 47:1450–1457PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Fraunhofer Institute for Molecular Biology and Applied Ecology IMEAachenGermany
  2. 2.Institute for Molecular BiotechnologyRWTH Aachen UniversityAachenGermany

Personalised recommendations