PROTEIN PRODUCTS FOR FUTURE GLOBAL GOOD
PLANTIGENS [ Plant Antigens ] are those Plant substances which cause Human/Animal production of Antibodies
PLANTIBODIES [Plant Antibodies ] are the Human/Animal Antibodies made by and in Transgenic Plants
We see, by 2020, a huge industry, Molecular farming the type of monoclonal antibody that is currently being produced. 5 years later we can easily see a fully Global industry worth in excess of $100 BILLION, Molecular farming the types of ''fully human'' monoclonals being created at this moment by Medarex and Abgenix.
From SCIENTIFIC AMERICAN ©.
Down a country road in southern Wisconsin lies a cornfield with ears of gold. The kernels growing on these few acres could be worth millions--not to grocers or ranchers but to drug companies. This corn is no Silver Queen, bred for sweetness, but a strain genetically engineered by Agracetus in Middleton, Wis., to secrete human antibodies. This autumn a pharmaceutical partner of Agracetus's plans to begin injecting cancer patients with doses of up to 250 milligrams of antibodies purified from mutant corn seeds. If the treatment works as intended, the antibodies will stick to tumor cells and deliver radioisotopes to kill them.
Using antibodies as drugs is not new, but manufacturing them in plants is, and the technique could be a real boon to the many biotechnology firms that have spent years and hundreds of millions of dollars trying to bring these promising medicines to market. So far most have failed, for two reasons.
First, many early antibody drugs either did not work or provoked severe allergic reactions. They were not human but mouse antibodies produced in vats of cloned mouse cells. In recent years, geneticists have bred cell lines that churn out antibodies that are mostly or completely human.These chimeras seem to work better :this past July one made by IDEC Pharmaceuticals passed scientific review by the Food and Drug
The new drug may be effective, but it will not be cheap; cost is the second barrier these medicines face. Cloned animal cells make inefficient factories: 10,000 liters of them eke out only a kilogram or two of usable antibodies. So some antibody therapies, which typically require a gram or more of drug for each patient, may cost more than insurance companies will cover. Low yields also raise the expense and risk of developing antibody drugs.
This, Agracetus scientist Vikram M. Paradkar says, is where "plantibodies" come in. By transplanting a human gene into corn reproductive cells and adding other DNA that cranks up the cells' production of the foreign protein, Agracetus has created a strain that it claims yields about 1.5 kilograms of pharmaceutical-quality antibodies per acre of corn. "We could grow enough antibodies to supply the entire U.S. market for our cancer drug--tens of thousands of patients--on just 30 acres," Paradkar predicts. The development process takes about a year longer in plants than in mammal cells, he concedes. "But start-up costs are far lower, and in full-scale production we can make proteins for orders of magnitude less cost," he adds.
Plantibodies might reduce another risk as well. The billions of cells in fermentation tanks can catch human diseases; plants don't. So although Agracetus must ensure that its plantibodies are free from pesticides and other kinds of contaminants, it can forgo expensive screening for viruses and bacterial toxins.
Corn is not the only crop that can mimic human cells. Agracetus is also cultivating soybeans that contain human antibodies against herpes simplex virus 2, a culprit in venereal disease, in the hope of producing a drug cheap enough to add to contraceptives.The web-shy Planet Biotechnology in Mountain View, Calif., is testing an anti-tooth-decay mouthwash made with antibodies extracted from transgenic tobacco plants. CropTech in Blacksburg, Va., has modified tobacco to manufacture an enzyme called glucocerebrosidase in its leaves. People with Gaucher's disease pay up to $160,000 a year for a supply of this crucial protein, which their bodies cannot make.
"It's rather astounding how accurately transgenic plants can translate the subtle signals that control human protein processing," says CropTech founder Carole L. Cramer. But, she cautions, there are important differences as well. Human cells adorn some antibodies with special carbohydrate molecules. Plant cells can stick the wrong carbohydrates onto a human antibody. If that happens, says Douglas A. Russell, a molecular biologist at Agracetus, the maladjusted antibodies cannot stimulate the body into producing its own immune response, and they are rapidly filtered from the bloodstream. Until that discrepancy is solved, Russell says, Agracetus will focus on plantibodies that don't need the carbohydrates. Next spring the company's clinical trial results may reveal other differences as well.
From TRENDS in Plant Science May 2001, Vol.6 No.5 [page220] © Elsevier Science
Therapeutic and diagnostic plantibodies; --
KEY - Application and specificity - Signal sequences - Antibody name or type - PLANT
Dental caries; streptococcal - Murine IgG signal peptides - Guys 13 (Secretory IgA) - Nicotiana Tabacum
Diagnostic; anti-human IgG - Murine IgG signal peptides - C5-1 (IgG) - ALFALFA
Cancer treatment; carcinoembryonic antigen - Murine IgG signal peptide; KDEL - ScFvT84.66 (ScFv) - WHEAT
Cancer treatment; carcinoembryonic antigen - Murine IgG signal peptide; KDEL - ScFvT84.66 (ScFv) - RICE
Cancer treatment; carcinoembryonic antigen
- TMV leader; murine IgG signal peptides; KDEL
- T84.66 (IgG)
- Nicotiana tabaccum (transiently with Agrobacterium
Herpes simplex virus 2 - Tobacco extensin signal peptide - Anti-HSV-2 (IgG) - SOYBEAN
ACTIN Press Release
At a conference in York last week, delegates from Europe, USA and New Zealand learned of new developments in the use of plants as providers of both natural and genetically modified products for the pharmaceutical and healthcare industries
Plants are already a valuable source of lead compounds for the pharmaceutical industry. According to Melanie O'Neill of Glaxo Wellcome's Medicines Research Centre, 8 of the top 30 medicines are natural products or semisynthetics with a value of $15.9bn in 1999. However, there is a continuing drive to discover new medicines for diseases that are poorly treatable and compounds with novel mechanisms of action.
The seminar learned how plants could provide such new lead compounds, new plant extracts and new combinations of genes, and also provide a delivery mechanism for therapeutic recombinant proteins and vaccines with benefits for developing countries.
Neil Robinson of MolecularNature illustrated the rich diversity of the British flora in providing new leads for the pharmaceutical, healthcare and agrochemical industries. Based at IGER (Institute for Grassland and Environmental Research) in Aberystwyth, MolecularNature is developing advanced chemical fingerprinting techniques for the isolation of rare natural compounds with biologically relevant structures. Of the 250,000 plant species that exist on our planet, only about 38,000 have been studied phytochemically and, perhaps, only 2% of plants have been thoroughly evaluated as a source of new medicines. Aspirin from willow, Digitalis from foxglove, for the treatment of cardiac conditions, and the anti-cancer activity of Taxol from yew are the tip of the iceberg.
At the molecular level, John Bedbrook of Maxygen, USA explained how the application of his companies MolecularBreedingTM technique of 'DNA shuffling' could produce novel compounds in plants. This technique has yielded enzymes with improved kinetics, altered substrate specificities, altered optima and selectivity of optima. Also at the molecular level, but with a global perspective, Julian Ma of Guy's Hospital described how using plants as the expression system for antibodies, antigens and immune complexes could make vaccines more widely affordable in developing countries. 'Plants are the most efficient producers of protein on the planet, with simple nutritional requirements and the potential to be grown on an agricultural scale'. As a dentist, his work is currently focused on the development of monoclonal antibodies in topical passive immunotherapy applications. However, the technology has far reaching potential.
Organised by ACTIN (Alternative Crops Technology Interaction Network) and the University's Plant Protein Club, the seminar may have been the first time that organisations interested in developing recombinant and endogenous plant products have met under the same roof! However, Ian Bartle, ACTIN Chief Executive, expressed the wish that the event would lead to a longer term dialogue between people who have one thing in common, namely the belief that plants are a safe and cost effective delivery system for many high value products for today's market.
More on plantibodies from the University of Arizona HERE