www.checkbiotech.org ; www.raupp.info ; www.czu.cz

Researchers working at Thomas Jefferson University in Philadelphia
demonstrated that an antibody produced in tobacco plants has the same
anticancer drug efficiency as conventionally produced antibodies, September
2006 by Daniela Kenzelmann, Checkbiotech.

A new generation of anti-cancer agents exploits the biological function of
antibodies, which is to specifically recognize and bind to their target.
There are different ways in which antibodies can help to fight cancer. One
way is that when an antibody binds to its target, it can block a biological
function of the target which is essential for cancer cell survival; or
antibody binding to a target on cancer cells, which acts as a marker to
recruit the immune system that in turn will destroy the cancer cells. Yet
another alternative is to arm antibodies with drugs, allowing site-specific
drug delivery.

The demand for therapeutic antibodies is growing quickly, but so far
production involving cell culture and genetically modified animals is
expensive and yields only limited amounts of product. The goal of Professor
Koprowskis? group was to prove that such antibodies can alternatively be
produced in plants at a much larger scale.

As a starting point, the researchers chose an antibody known to recognize
the Lewis Y antigen and to be effective in cancer treatment. The so-called
Lewis Y oligosaccharide is found in large quantities on the surface of
breast, lung, ovary and colon cancer cells and is thus a good target for
these types of cancers.

First, the researchers engineered tobacco plants so that they could produce
the desired antibody. Then they purified the Lewis Y specific antibody from
the leaves of the tobacco plants. Next, Dr. Koprowski laboratory compared
the plant-produced antibody to the one that was produced through more
traditional methods. This is important because plants add slightly different
sugar chains to proteins than mammalian cells do, which can sometimes change
the effectiveness of an antibody.

On one hand, it was necessary to ensure efficient binding to Lewis Y, and
equally important, the researchers also had to confirm that the plant-made
antibody was able activate the immune system. For a final proof of activity,
the researchers demonstrated the ability of the plant-derived antibody to
kill human tumors that had been transplanted and allowed to grow in mice.

In all these experiments, the plant-derived antibody performed as well as
the conventionally produced antibody. The work from Dr. Koprowski?s team
clearly indicates that genetically modified plants are a suitable source for
therapeutic antibodies, and more importantly, they are also able to
stimulate the immune system to kill cancer cells.

?If appropriate funding is provided, clinical trials are already possible
within one year or less,? says Dr. Steplewski, a researcher in Dr. Koprowski
?s team. He believes antibody immunotherapy will be very useful to treat
cancer patients after surgery to prevent tumor recurrence. At the moment,
there is already a conventionally produced Lewis Y antibody coupled to the
cancer drug doxorubicin in clinical trial phase II.

?Now it is possible to produce cancer drugs and also vaccines against viral
and bacterial infections, inexpensively and in large quantities using gene
technology in plants,? adds Dr. Steplewski. ?I hope that the public will
learn to see not only the potential risks of this field of science, but also
the benefits. Production of biomedicines in plants lowers the costs fifty
times, which would also be particularly advantageous for developing
countries.?

This work is already the second study from Dr. Koprowski?s group proving
that plant-derived antibodies are effective cancer immunotherapy agents. In
the future, plant gene technology could become the method of choice to
produce therapeutically active proteins due to their numerous advantages
over conventional methods.

Daniela Kenzelmann is a Science Journalist for Checkbiotech and is writing
her PhD at the Friedrich Miescher Institute in Basel, Switzerland. Contact
her at daniela.kenzelmann@fmi.ch

Brodzik et al. Plant-derived anti-Lewis Y mAb exhibits biological activities
for efficient immunotherapy against human cancer cells. PNAS, 2006

[www.ncbi.nlm.nih.gov]
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