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Senior Citizen Health & Medicine
Vaccine that Stops Cancer in Mice is Headed for
Human Clinical Trial Soon
When we tested our best vaccine we got really,
really fabulous antibody levels that have never been seen before
 Oct. 29, 2007 Tantalizing news of a big step
forward in the development of a vaccine to stop cancer has been
announced by researchers at the University of Georgia Cancer Center.
Backed by the National Cancer Institute, the scientists have created a
carbohydrate-based vaccine that in mice has successfully triggered a
strong immune response to cancer cells.
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When cells become cancerous, the sugars on their
surfaces undergo distinct changes that set them apart from healthy
cells. For decades, scientists have tried to exploit these differences
by training the immune system to attack cancerous cells before they can
spread and ravage the body.
These findings, published in the October issue of
the journal Nature Chemical Biology, brings the scientists one step
closer to a much-sought-after cancer vaccine.
In mice we can illicit very strong antibody
responses and we have shown that the antibody responses are functional
that they can kill cancer cells, said lead author Geert-Jan Boons,
Franklin professor of chemistry.
Vaccines are currently used to prevent diseases by
priming the immune system to recognize and attack a virus or bacteria.
The vaccine that Boons and his team have developed, on the other hand,
is a therapeutic vaccine that trains the bodys immune system to fight
an existing disease.
The discovery in the 1970s of unique sugars on
cancer cells set scientists in search of a way to get the immune system
to recognize and attack cells that express these cancer-associated
sugars. Until now, however, the results have been less than spectacular.
Cancer cells originate in the body, and the immune
system leaves them alone because it distinguishes between the bodys own
cells and foreign invaders such as viruses and bacteria.
Boons explained that early cancer vaccines were
created by linking the tumor-associated carbohydrate with a foreign
protein. The immune system, perhaps not surprisingly, attacked the
protein and the linker molecules, but generally left the carbohydrate
alone.
We needed to come up with a vaccine that does not
give our immune system a chance to go after anything else but the
tumor-associated carbohydrate, Boons said. In other words, there
should no junk that can induce an immune response to something other
than the tumor-associated carbohydrate.
Rather than using naturally derived and purified
proteins and linkers, Boons and his team created a vaccine synthetically
from scratch by stacking molecules together and arranging them in the
appropriate configuration.
In 2005, they created a fully synthetic vaccine
that stimulated an immune response to the tumor-associated carbohydrate
alone. The vaccine stimulated only low antibody levels, however, so the
researchers began optimizing the components of the vaccine to illicit a
stronger immune response.
Their optimized vaccine includes a tumor-associated
carbohydrate that triggers the immune systems B cells, a part of a
protein that triggers the immune systems T cells and a linker molecule
that stimulates the production of generalized immune components known as
cytokines.
The results of their three-pronged approach were
astounding, particularly with respect to a critical component of the
immune system known as IgG.
When we tested our best vaccine we got really,
really fabulous antibody levels that have never been seen before, Boons
said. The levels of IgG antibody production were 100 times better than
with conventional approaches.
The vaccine has been successful in creating an
antibody response that can kill cultured epithelial cells those
commonly involved in most solid tumors, such as breast and colorectal
cancer derived from mice and in stimulating an immune response in
healthy mice.
The researchers are currently testing the vaccine
in mice with cancer, and Boons hopes to start phase I clinical trials in
humans within a year.
Despite his enthusiasm for his work, Boons cautions
that its too early to predict how the vaccine will perform in humans.
Theres a very big step going from mice to
humans, he said. Other cancer vaccines have worked in mice but not in
humans.
In addition to testing the new vaccine, Boons team
is exploring the specific components of the immune response as they
relate to cancer, determining the exact cytokines and antibodies that
are most effective against cancer cells.
Were looking at which molecules are being
upregulated at each level of immune response, Boons said. That gives
us a road map to further optimize each component of the vaccine.
The research is supported by the National Cancer
Institute.
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