Cambridge Healthtech Institute recently spoke with leading experts and speakers from the plant-made pharmaceuticals (PMP) industry about some of key talking points at CHI’s inaugural Plant-based Expression and Synthetic Biology conference, taking place January 10-11, 2017 as part of the 16th Annual PepTalk event which runs from January 9- 13, 2017 in San Diego, CA.
Roundtable Participants:
Karen A. McDonald, Ph.D., Professor, Chemical Engineering, University of California, Davis
Elizabeth E. Hood, Ph.D., CEO, Infinite Enzymes, LLC, Distinguished Professor of Agriculture, Arkansas State University
Julian Ma, Ph.D., Hotung Chair of Molecular Immunology, Institute for Infection and Immunity, St. George’s Hospital Medical School, University of London
Nobuyuki Matoba, Ph.D., Associate Professor, Department of Pharmacology and Toxicology, James Graham Brown Cancer Center, University of Louisville School of Medicine
Q: Why is plant made biopharmaceuticals such an exciting field to be part of at the moment?
Karen McDonald: The plant-made pharmaceuticals (PMP) field is a tremendously exciting field to be a part of, not only because of new scientific and engineering developments that illustrate the potential of the technologies, but also because PMP products have now been commercialized and large-scale production facilities are now in operation. CRISPR technologies also have great potential in this field in terms of creating “designer hosts” and for the production of small molecule products.
Elizabeth Hood: Using plants to manufacture drugs and industrial chemicals is a technology that holds tremendous promise. It is an obvious link between human health and plants that has not been fully appreciated in the past. In addition, being able to manufacture industrial chemicals and biobased products allows environmental advantages that are unprecedented. The concept of drugs without contaminants from animal cell culture or native sources speaks broadly to safety concerns. These products and drugs can be orally delivered and stored without a cold chain when formulated from edible plant materials. Additionally, the concept of biobased products allows humans to use renewable materials for manufactured goods through sustainable processes. New technologies such as genome sequencing and CRISPR/cas9 gene editing are opening many new avenues for making giant leaps forward with products and volumes of plant materials. This entire field is poised for great things in the next 20 years, which is excellent considering the many challenges for humankind and the environment.
Julian Ma: Many reasons – plant made biopharmaceuticals entered the public consciousness in 2015 when ZMapp, a cocktail of three monoclonal antibodies produced in plants, was provided for emergency use against Ebola infection. But there have been a number of other recent advances, including a GMP manufacturing license issued in Europe for a tobacco plant manufacturing process, a number of plant made biopharmaceuticals in clinical trials, and two commercial products. So, the field is gathering momentum.
Nobuyuki Matoba: Because of plants- they offer a number of unique opportunities that other recombinant production platforms cannot. The technology is, however, still at an early stage- We have not yet been able to fully exploit their capacity.
Q: What will delegates gain by attending your session?
KM: Delegates will learn about the different ways in which plants can be used as hosts for recombinant protein production (including transient production using indoor-grown plants and plant cell cultures grown in bioreactors), quality attributes and regulatory requirements of plant-made biologics, host engineering and removal of host cell proteins.
EH: My presentation: Plant-Based Production of Industrial Proteins: will address issues in large scale production of industrial products, particularly enzymes. Low cost is a primary factor and this talk will follow several others that discuss limitations on production that affect cost. One of the most important is high protein accumulation in biomass, which is affected by numerous molecular and genetic factors, which will be discussed.
JM: They will get up to date with the field, learn about the most advanced biotechnologies and the advantages they bring to biologic manufacture, understand the regulatory landscape, and hear opinions of leaders in the field regarding where plantmade biopharmaceuticals will make an impact I the future.
NM: Utilizing plant-based systems to facilitate protein engineering.
Q: Which technology, research or paper has really excited you recently?
KM: As a bioprocess engineer I’m particularly excited about publications that describe commercial large-scale PMP facilities such as:
- Pogue, G.P.; Vojdani, F.; Palmer, K.E.; Hiatt, E.; Hume, S.; Phelps, J.; Long, L.; Bohorova, N.; Kim, D.; Pauly, M., et al. Production of pharmaceutical-grade recombinant aprotinin and a monoclonal antibody product using plant-based transient expression systems. Plant biotechnology journal 2010, 8, 638-654.
- Klimyuk, V.; Pogue, G.; Herz, S.; Butler, J.; Haydon, H. Production of recombinant antigens and antibodies in nicotiana benthamiana using ‘magnifection’ technology: GMP-compliant facilities for small- and large-scale manufacturing. In Plant viral vectors, Palmer, K.; Gleba, Y., Eds. Springer Berlin Heidelberg: Berlin, Heidelberg, 2012; pp 127-154.
- Holtz, B.R.; Berquist, B.R.; Bennett, L.D.; Kommineni, V.J.; Munigunti, R.K.; White, E.L.; Wilkerson, D.C.; Wong, K.Y.; Ly, L.H.; Marcel, S. Commercial-scale biotherapeutics manufacturing facility for plant-made pharmaceuticals. Plant biotechnology journal 2015, 13, 1180-1190.
- Tekoah, Y.; Shulman, A.; Kizhner, T.; Ruderfer, I.; Fux, L.; Nataf, Y.; Bartfeld, D.; Ariel, T.; Gingis–Velitski, S.; Hanania, U., et al. Large-scale production of pharmaceutical proteins in plant cell culture—the protalix experience. Plant Biotechnology Journal 2015, 13, 1199-1208.
- Lomonossoff, G.P.; D’Aoust, M.-A. Plant-produced biopharmaceuticals: A case of technical developments driving clinical deployment. Science 2016, 353, 1237-1240.
Our group has also developed techno-economic models for PMP facilities with simulation files that are available to the community so that they can implement their own process assumptions to estimate capital investment and manufacturing costs for PMP:
- Tusé, D.; Tu, T.; McDonald, K.A. Manufacturing economics of plant-made biologics: Case studies in therapeutic and industrial enzymes. BioMed Research International 2014, 2014, 16.
- 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, 1456-1466.
EH: Although I have been a proponent of genetic engineering for 35 years, it is a technology that has received tremendous push-back from the public at large and from certain lobby groups. Thus, the new gene editing technology encompassed by CRISPR/Cas9 has presented a mechanism that is palatable to many that may allow us to by-pass the controversy over new products produced through genetic engineering. I’m excited to use this mechanism to produce new products for animal health and industry.
NM: Germline-targeting vaccine strategy
Q: Why are you attending PepTalk and what are you looking forward to at 2017’s gathering?
KM: I’m attending to hear about exciting new developments in recombinant protein production. I’m looking forward to the first Plant Based Expression and Synthetic Biology session at PepTalk butalso the breadth of talks related to cell line development, protein engineering, production, purification, and analytics for recombinant protein production.
EH: The molecular farming industry used to have regular meetings among the community of researchers and we were able to network and receive annual updates. However, that community has been dealt some heavy blows through the anti-GMO atmosphere of the general public and our meetings have dwindled. Thus, I am very excited to visit with friends in the industry and be updated on all the latest research and progress with product development.
Q: Do you have a special talent or fact the audience might not know about you?
EH: The plant transformation DNA delivery vehicle, Agrobacterium tumefaciens strain EHA101, was my PhD project. It is used in 1000’s of labs worldwide for transformation of a wide variety of plants, including many recalcitrant ones.
To Learn More About The Conference and Peptalk, Visit:
CHI-PepTalk.com/Plant-Based-Expression-Conference
Karen A. McDonald, Ph.D., Professor, Chemical Engineering, University of California, Davis
Dr. McDonald is a Professor of Chemical Engineering at the University of California at Davis and currently serves as the Faculty Director of the UC Davis ADVANCE Institutional Transformation program, an NSF funded program to improve the recruitment, retention and advancement of women STEM faculty. She received her BS from Stanford University, her MS from the University of California, Berkeley and her Ph.D. from the University of Maryland, College Park, all in Chemical Engineering. Professor McDonald’s research is at the interface of plant synthetic biology and bioprocess engineering, utilizing novel protein expression systems for production of human therapeutics and industrial enzymes in plant tissues and plant cell culture bioreactor systems. From 2006-2013, she was the PI and Director of the NSF CREATE-IGERT, an interdisciplinary graduate training program with a focus on applications of plant biotechnology to biopharmaceuticals, biorefineries and sustainable agriculture. Her research has generated over 70 referred journal articles, three issued patents and three patent applications in plant-based expression of recombinant proteins, with practical applications in human therapeutics, subunit vaccines, biodefense agents and biomaterials for medical applications. She is also a cofounder of Inserogen, Inc., a plant biotechnology startup focused on production of therapeutics for neglected or underserved orphan and rare diseases.
Julian Ma, Ph.D., Hotung Chair of Molecular Immunology, Institute for Infection and Immunity, St. George’s Hospital Medical School, University of London
Professor Julian Ma is the Hotung Chair of Molecular Immunology and Director of the Institute for Infection and Immunity at St. George’s, University of London, and honorary Consultant in Oral Medicine at King’s College London. He graduated in dentistry at Guy's Hospital in 1983, and went on there to gain his Ph.D. in Immunology, studying topical anti-microbial immunotherapy using monoclonal antibodies. His research group studies basic mechanisms of protein assembly, processing and expression in plant cells, as well as the design, engineering and clinical applications of novel recombinant proteins in plants for systemic and mucosal vaccination and immunotherapy. Disease targets focus on infectious diseases that predominantly affect the poor in developing countries, including HIV, rabies and TB. Julian Ma is a leading proponent in Europe for the development of plant biotechnology for medicines for human health.
Nobuyuki Matoba, Ph.D., Associate Professor, Department of Pharmacology and Toxicology, James Graham Brown Cancer Center, University of Louisville School of Medicine
Dr. Nobuyuki Matoba received his Ph.D. degree in Applied Life Science from Kyoto University, Japan. He is an Associate Professor (with tenure) of Pharmacology & Toxicology and a Principal Investigator of the Owensboro Cancer Research Program within James Graham Brown Cancer Center at University of Louisville School of Medicine. Before joining the UofL faculty, he had been a Japan Society for Promotion of Science (JSPS) Research Fellow, a JSPS Postdoctoral Fellow for Research Abroad, and a Research Assistant Professor at Arizona State University Biodesign Institute. He currently serves on the editorial board of the journal Scientific Reports. Dr. Matoba’s research is focused on the development of plant-made protein pharmaceuticals. In particular, he is interested in engineering subunit vaccines and biotherapeutics against mucosal diseases/pathogens. His laboratory is currently developing two classes of unique protein pharmaceuticals: (1) lectibodies targeting viral and tumor-associated glycan biomarkers; and (2) mucosal immunomodulators/vaccines based on bacterial toxin subunits.