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© PhD Students Symposium 2005. All rights reserved.
Charles J. Arntzen, PhD
Biodesign Institute, Arizona State University, United States of America
My primary message is that plant biotechnology can be used for production
of pharmacologically active proteins, and that this system will be useful
for traditional pharmaceutical manufacturing - but also for overcoming
health and agricultural constraints in the developing world. Members of
our Center for Infectious Disease and Vaccinology in the Biodesign
Institute of Arizona State University are strongly committed to finding new
protein manufacturing that is directly applicable to programs of public
health in poor countries, especially for subunit vaccines. We also believe
in public/private partnerships to achieve technology transfer that will
allow manufacture of new protein pharmaceuticals in developing countries to
to fight infectious diseases that are of major importance to their
citizens.
In the last decade, our team of researchers has played a major role in
showing that plant biotechnology is a promising platform for novel
pharmaceutical protein biomanufacture. Green plants have emerged as a
convenient, safe and economical alternative to microbial and animal cell
fermentation or transgenic animals for the production of clinically useful
proteins; plants have particular advantages for avoidance of capital cost
investment when large quantities of product are needed (thousands of
kilograms of protein, for example). Most plant-derived product development
effort is focused upon monoclonal antibodies (IgG, IgA, secretory IgA),
subunit vaccines, and enzymes. Clinical trials have been approved by the
US FDA for several plant-derived vaccines, including four trials of non-
processed plant tissue fed to humans (sometimes called edible vaccines),
and for cancer vaccines purified from tobacco leaf tissue. Regulatory
approval has also been achieved for human testing of plant-derived enzymes
(as will be discussed by other speakers at this conference).
My presentation will summarize recent advancements in technology to produce
pharmaceuticals in plants, and non-technical constraints that can slow the
movement of these products into the market place. Principal among the
constraints is uncertainty on how regulatory agencies will allow testing
and licensure of plant-made pharmaceuticals. I will discuss the findings
of a WHO informal consultation on scientific basis for regulatory
evaluation of candidate human vaccines from plants, that was held in
Geneva, Switzerland on 24-25 January 2005; the summary conclusion is that
there are many precedents for extraction of non-protein pharmaceuticals
from plants (anticancer agents, ginseng, etc.), and that existing
regulatory systems are appropriate to adapt to new protein pharmaceuticals.
For protein drugs, I will utilize two completed studies (production of a
subunit plague vaccine and a human enzyme) to demonstrate the effectiveness
of plants as a production system. My discussion will include how our
academic research center has invested in facilities and personnel to move
prototype products from basic science through cGMP bioprocessing to produce
prototype products derived from plants, with a strong focus on needs for
products for the developing world.
In this presentation I will utilize data and ideas derived from many of my
colleagues in our Center, including Hugh Mason and Tsafrir Mor (formerly
with the Boyce Thompson Institute at Cornell), Guy Cardineau (formerly with
Dow AgroSciences), Steve Slater (formerly with Monsanto), Richard Mahoney
(formerly with the International Vaccine Institute in Seoul), and Anatole
Krattiger (formerly with Cornell).