More evidence of tobacco’s role as drugmaking factory
pharmafile | August 27, 2009 | News story | Manufacturing and Production, Research and Development |Â Â Biodesign InstituteÂ
Researchers have successfully engineered tobacco to synthesise the antigens for a vaccine against norovirus, providing further evidence that complex pharmaceuticals can be made in transgenic plants.
The team, from the Biodesign Institute at Arizona State University in the US, say they will soon be ready to start clinical trials of the vaccine, which will protect against a group of viruses that are a major cause of gastroenteritis in humans.
The team used a tobacco mosaic virus that was re-engineered to produce high levels of virus-like particles (nanoparticles) containing the vaccine antigen in tobacco plants in just one to two weeks, a remarkably short time-frame compared to other recombinant production techniques. Gram quantities suitable for clinical testing can be made in eight to 10 weeks, with full commercial-scale production in as little as four months.
That is an important factor for norovirus, because this type of virus mutates so quickly it can be hard for vaccine developers to keep up. That rate of mutation has held back efforts to develop a vaccine in the past.
Charles Arntzen, who led the team and presented the research at the American Chemical Societys national meeting in Washington DC earlier this week, said the challenge now it to establish manufacturing protocols that meet pharmaceutical standards needed for human clinical trials.
The team plans to start testing a nasal spray formulation of the vaccine in human subjects later in the year with the help of the US National Institutes of Health (NIH).
Making drugs in transgenic plants and animals offer the tantalizing prospect of producing therapeutic proteins at large-scale and low-cost, but has so far largely failed to live up to early expectations.
In the early years of the decade market researchers were predicting a multibillion dollar market for products made by transgenic manufacturing, but to date only one medicine made in this way – GTC Biotherapeutics/Lundbecks Atryn (recombinant antithrombin) which is made in the milk of goats – has actually reached the market.
One issue has been that regulators have set the bar very high for approval of transgenic medicines. Atryn itself was turned down for approval in Europe in February 2006, seven months before a green light was eventually given, because it wanted data on more patients. It took almost three years more for the drug to be approved in the USA.
Other obstacles include the strict containment measures needed to make sure transgenic genes do not escape into the environment, the controversy over genetic modification of plants and animals used as food, and technical issues relating to expressing, extracting and purifying the protein material.
Now there are signs that these issues are being overcome and Arntzen believes that work in this area is accelerating and 2009 and 2010 could mark a turning point fort the technology.
For example, last year Bayer set up a pilot-scale production facility in Halle, Germany, that will use engineered tobacco plants to make proteins, initially in growth media then transferred to greenhouses for large-scale production. Bayer has acquired a technique which allows wild-type tobacco plants to be engineered quickly via an acute viral infection, rather than relying on time consuming crop development approaches.
There are also a number of other academic teams looking at the use of tobacco for protein production.
Earlier this year, a team of European scientists led by Professor Mario Pezzotti at the University of Verona successfully made interleukin-10 in tobacco plants at levels that could support use of the plant leaves themselves as the drug delivery vehicle, without the need for lengthy extraction and purification procedures.
Last year, a team at Stanford University and Large Scale Biology Corp in the US reported phase I results from a trials of a therapeutic vaccine for follicular B cell lymphoma made in tobacco plants. In this case the rapid production achievable with tobacco made it possible to develop a therapy that was personalised to each patient based on the antigenic nature of their own cancer.
