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A new therapeutic vaccine under development for melanoma-one
of the most deadly forms of skin cancer-offers hope of killing
the disease.
Zhongwu Guo, CWRU assistant professor of chemistry, is the lead
researcher on a five-year, $1.1 million National Institutes of
Health research project, "Metabolic Engineering of Cancer for
Immunotargeting." His CWRU co-investigators are Clifford Harding,
professor of pathology, and Lili Liu, associate professor of oncology,
both from the CWRU School of Medicine, with Stanton Gerson, professor
of oncology, serving as the project's consultant.
Melanoma occurs when tumors start to grow on clusters of the
melanocytes that produce melanin or skin color. Sometimes these
clusters appear as moles, which are benign. When moles turn darker
or begin to grow, it is sometimes a sign of cancer and should
be tested.
While a researcher at the National Research Council in Canada
before coming to CWRU two years ago, Guo worked on a project that
developed a vaccine for leukemia. He plans to employ the same
theories to the melanoma. "Developing vaccines for therapy is
very popular now," Guo said. He points out that while the idea
for cancer vaccines is more than 100 years old, it has seen a
revival of interest.
Instead of preventative vaccines, which are usually administered
to protect against special bacterial diseases, Guo prefers the
term immunotherapy to describe the cancer vaccines that clean
up a disease after it appears. Once he can establish that procedure,
he says that theory or process will have applications to other
cancers as well. On the surface of cancer cells are abnormal tumor-associated
carbohydrate antigens (TACAs) normally not found on non-cancerous
cells.
He likens these antigens to the cancer's fingerprint, which is
different for each cancer. He said once researchers know the right
antigens, they will have the key to unlocking a cure. In melanoma,
these antigens are called GD2, GD3, GM2 and GM3.
According to Guo, it is difficult to construct effective vaccines
from these antigens directly because the immune systems of cancer
patients develop immune tolerance to the natural antigens. Guo
and his collaborators proposed a new strategy to get around the
problem.
How the new vaccine works, according to Guo, is to first boost
the body's immune system with a synthetic vaccine made of an artificially
modified TACA and then trigger the cancer cells to express this
artificial antigen by treating the patient with a synthetic precursor.
Because the synthetic antigen is foreign to the immune system,
it does not have the immune tolerance that the naturally occurring
TACAs have, and an immune response can be easily established to
it. Once the tumor cells are marked by the modified TACA, the
pre-stimulated immune system will react to them and wipe them
out. In the lab, mice with melanoma are given the synthetic vaccine
to boost the immune system.
Researchers check the mice daily for their level of the immune
response until the mice are primed to receive the precursor. Once
administered, the precursor will be used by the cancer cells to
present the modified antigen through their TACA biosynthetic machinery.
Then the immune system goes to work. The prime goal of the project,
Guo said, is to find the proper combination of the precursor and
vaccine for melanoma.
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