- 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.
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- 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.
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- 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.
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- 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."
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- 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.
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- 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.
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- "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."
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- A report on the research is being published in the advance
online edition of the journal Nature Biotechnology.
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- 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.
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- 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.
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- "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.
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- 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.
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- 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."
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- 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.
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- 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.
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- Previously, mice were cloned to produce human antibodies,
but cows offer the advantage of producing very large numbers of antibodies,
according to the report.
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- SOURCE: Nature Biotechnology 2002;10.1038/nbt727.
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