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Cloned Cows Produce Human Antibodies
By Merritt McKinney
8-12-2

NEW YORK (Reuters Health) - Scientists in Japan and the US have cloned cows that produce human antibodies, an achievement that holds promise for treating certain diseases.
 
While researchers have produced human antibody-generating mice, cows can produce much larger quantities. However, more work needs to be done before the antibodies can be used in humans. Researchers must purify the human antibodies from cow proteins and ensure that the final product is free of animal viruses.
 
Though the process of using cows as antibody factories is still in the early stages, the approach may avoid several of the difficulties in making sufficient quantities of the antibodies.
 
Dr. James M. Robl, the president and chief scientific officer of Hematech, the South Dakota biotechnology company that conducted the research with the Japanese brewing company Kirin, told Reuters Health, "Hematech and Kirin have successfully transferred a major component of the human immune system into cows. This gives us the ability to produce a wide variety of complex, natural therapeutics that will help people to fight many different kinds of disease."
 
According to Robl, the product produced by the cows is a complex mix of antibodies known as polyclonal antibodies that can be used as a supplement to or substitute for antibiotics, antiviral compounds and vaccines.
 
Polyclonal antibodies are currently derived from donated human blood and are infused into patients to help fight infection. Polyclonal antibodies are used in a variety of patients, typically those who need the immune system boost, and such patients could theoretically be candidates for the cow-derived product.
 
"It would be particularly useful," Robl said, "for patients who have difficulty fighting disease, such as children, the elderly, patients recovering from trauma or surgery, organ transplant patients and individuals with certain kinds of genetic defects."
 
A report on the research is being published in the advance online edition of the journal Nature Biotechnology.
 
Using cows to produce polyclonal antibodies may avoid some of the problems that currently limit their supply, Dr. Yann Echelard of GTC Biotherapeutics, Inc. in Framingham, Massachusetts, told Reuters Health.
 
According to Echelard, who was not involved with the research, human antibodies called gamma-globulins or intravenous immunoglobulins (IVIGs) are used to treat many conditions, including autoimmune diseases and some infections. Right now, these IVIGs are collected from pooled blood from human donors, Echelard said.
 
"This limits supply and also creates risk of transmission of infections," he pointed out. "With cows, one would be able to overcome supply issues, reduce infectious risk and create even better IVIGs by immunizing the cows with specific targets," such as HIV, the virus that causes AIDS.
 
But for the process to be practical, Echelard said that it is "very likely" that the cows' own antibody genes will have to be deactivated "so their expression does not interfere with the expression of the human genes. It should be very doable, but labor intensive." He added that it will be important to develop a purification process that is efficient at separating human antibodies from cow ones.
 
Robl also noted that the work is not over yet. He said, "The first step in the project, which we have accomplished, is to put the human immune system genes into cows. The second step, which is in progress, is to remove the cow immune system genes." Once both steps are completed, Robl said, "we will be ready for production."
 
Echelard noted that, as is the case with all new therapies, any antibodies derived from cows would have to undergo full clinical trials to prove their effectiveness.
 
In the experiments, Robl's team inserted an artificial human chromosome into fibroblasts--connective tissue cells--and used the cells to clone cow embryos. The chromosome carried the genes for two proteins that make human antibodies. The cloned embryos eventually formed four healthy calves that produced human antibodies in their blood.
 
Previously, mice were cloned to produce human antibodies, but cows offer the advantage of producing very large numbers of antibodies, according to the report.
 
SOURCE: Nature Biotechnology 2002;10.1038/nbt727.





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