Plant-produced biopharmaceuticals: A case of technical developments driving clinical deployment

The ability to express heterologous proteins in plants has led to the concept of using plants as “bioreactors” or “biofactories” for the production of pharmaceutical proteins. Although initial studies were promising, the pathway to commercialization and deployment in a clinical setting has proven to be a somewhat rocky road. This Review examines the technical developments that have led to the current increase in interest in the use of plants for the production of pharmaceutical proteins, particularly in the context of clinical trials.

[1]  G. Lomonossoff,et al.  When plant virology met Agrobacterium: the rise of the deconstructed clones , 2015, Plant biotechnology journal.

[2]  D. M. Lam,et al.  Expression of hepatitis B surface antigen in transgenic plants. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[3]  B. Yassine-Diab,et al.  Influenza virus-like particle vaccines made in Nicotiana benthamiana elicit durable, poly-functional and cross-reactive T cell responses to influenza HA antigens. , 2014, Clinical immunology.

[4]  J W Larrick,et al.  Antibody engineering at the millennium. , 2000, BioTechniques.

[5]  Lisa Hensley,et al.  Delayed treatment of Ebola virus infection with plant-derived monoclonal antibodies provides protection in rhesus macaques , 2012, Proceedings of the National Academy of Sciences.

[6]  M. Levine,et al.  Immunogenicity in humans of a recombinant bacterial antigen delivered in a transgenic potato , 1998, Nature Medicine.

[7]  토마스 라데마허 Method for the generation and cultivation of a plant cell pack , 2013 .

[8]  R. Levy,et al.  Plant-produced idiotype vaccines for the treatment of non-Hodgkin's lymphoma: Safety and immunogenicity in a phase I clinical study , 2008, Proceedings of the National Academy of Sciences.

[9]  Y. Gleba,et al.  Plant viral vectors for delivery by Agrobacterium. , 2014, Current topics in microbiology and immunology.

[10]  S. Streatfield,et al.  Antibody Production in Plants and Green Algae. , 2016, Annual review of plant biology.

[11]  J. Featherstone,et al.  Clinical Trial of a Plant-Derived Antibody on Recolonization of Mutans Streptococci , 2005, Caries Research.

[12]  G. Stiegler,et al.  Generation of glyco-engineered Nicotiana benthamiana for the production of monoclonal antibodies with a homogeneous human-like N-glycan structure. , 2008, Plant biotechnology journal.

[13]  L. Vézina,et al.  Human antibody response to N-glycans present on plant-made influenza virus-like particle (VLP) vaccines. , 2014, Vaccine.

[14]  A. Mehta,et al.  Pivotal trial with plant cell-expressed recombinant glucocerebrosidase, taliglucerase alfa, a novel enzyme replacement therapy for Gaucher disease. , 2011, Blood.

[15]  O. Dym,et al.  Production of glucocerebrosidase with terminal mannose glycans for enzyme replacement therapy of Gaucher's disease using a plant cell system. , 2007, Plant biotechnology journal.

[16]  J. Strong,et al.  Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp™ , 2014, Nature.

[17]  C. Oostenbrink,et al.  Expression and glycoengineering of functionally active heteromultimeric IgM in plants , 2014, Proceedings of the National Academy of Sciences.

[18]  G. Grabowski,et al.  Taliglucerase alfa: an enzyme replacement therapy using plant cell expression technology. , 2014, Molecular genetics and metabolism.

[19]  N. Bohorova,et al.  Enhanced potency of a fucose-free monoclonal antibody being developed as an Ebola virus immunoprotectant , 2011, Proceedings of the National Academy of Sciences.

[20]  T. Lehner,et al.  Generation and assembly of secretory antibodies in plants , 1995, Science.

[21]  R. Fischer,et al.  Overcoming low yields of plant‐made antibodies by a protein engineering approach , 2016, Biotechnology journal.

[22]  A. Hiatt,et al.  Production of antibodies in transgenic plants , 1989, Nature.

[23]  H. Mason,et al.  Oral immunization with a recombinant bacterial antigen produced in transgenic plants , 1995, Science.

[24]  G. Lomonossoff,et al.  Molecular pharming - VLPs made in plants. , 2016, Current opinion in biotechnology.

[25]  R. Collins,et al.  Clinical Safety and Immunogenicity of Tumor-Targeted, Plant-Made Id-KLH Conjugate Vaccines for Follicular Lymphoma , 2015, BioMed research international.

[26]  R. Naidu,et al.  Nicotiana benthamiana: its history and future as a model for plant-pathogen interactions. , 2008, Molecular plant-microbe interactions : MPMI.

[27]  Brian J. Ward,et al.  Preclinical and Clinical Development of Plant-Made Virus-Like Particle Vaccine against Avian H5N1 Influenza , 2010, PloS one.

[28]  J. Fox First plant-made biologic approved , 2012, Nature Biotechnology.

[29]  R. Schiffmann,et al.  Mannose receptor-mediated delivery of moss-made α-galactosidase A efficiently corrects enzyme deficiency in Fabry mice , 2015, Journal of Inherited Metabolic Disease.

[30]  E. Rybicki Plant-based vaccines against viruses , 2014, Virology Journal.

[31]  R. Twyman,et al.  Regulatory approval and a first-in-human phase I clinical trial of a monoclonal antibody produced in transgenic tobacco plants. , 2015, Plant biotechnology journal.

[32]  Rainer Fischer,et al.  The CRISPR/Cas9 system for plant genome editing and beyond. , 2015, Biotechnology advances.

[33]  B. Yassine-Diab,et al.  A plant-derived quadrivalent virus like particle influenza vaccine induces cross-reactive antibody and T cell response in healthy adults. , 2016, Clinical immunology.

[34]  D. Stuart,et al.  Tandem Fusion of Hepatitis B Core Antigen Allows Assembly of Virus-Like Particles in Bacteria and Plants with Enhanced Capacity to Accommodate Foreign Proteins , 2015, PloS one.

[35]  A. Depicker,et al.  Biomanufacturing of protective antibodies and other therapeutics in edible plant tissues for oral applications , 2016, Plant biotechnology journal.

[36]  Yoram Tekoah,et al.  Large-scale production of pharmaceutical proteins in plant cell culture-the Protalix experience. , 2015, Plant biotechnology journal.

[37]  M. Pauly,et al.  Emerging antibody-based products. , 2014, Current topics in microbiology and immunology.