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Thomas Kieber-Emmons,
Ph.D., is using the two machines in his
research on possible vaccines that will
give cancer patients better immunity
against recurrence of the disease. The
Biacore units are the first in Arkansas.
Scientists at UAMS will be able to use
them in research on other diseases, too.
By monitoring the progress
of biomolecular interactions in real time,
Biacore systems can provide answers to a
series of basic questions about
biomolecules and their interactions. That
technology has ramifications for a wide
range of cancer research, but is
especially important to the work of Kieber-Emmons,
who was recently recruited from the
University of Pennsylvania to UAMS as
director of basic breast cancer research
at the ACRC, is a professor of pathology
in the UAMS College of Medicine, and holds
the Josetta Edwards Wilkins Chair in
Breast Cancer Research in the college.
Kieber-Emmons, an
immunologist, is experimenting with
ways to affect a cellular response,
previously thought to only be possible in
reaction to protein antigens, to
carbohydrate antigens that are found on
cancer cells.
Antibodies can confront
carbohydrate antigens in the classic
immune response to rid the body of
bacteria, viruses, and some tumor cells.
But antibody immunity is not as effective
against tumor cells as cellular immunity,
in which T cells are activated to
recognize pieces of tumor antigen in order
to destroy the tumor. Carbohydrates are
processed by the immune system differently
than protein antigens, and therefore are
not typically recognized by the T cells.
“So what we’ve been doing
is figuring out the molecular structure of
carbohydrates and then recreating them
through computer generation into an amino
acid compound called a peptide,” Kieber-Emmons
said of his unique research. “In essence
it’s a protein antigen that mimics a
carbohydrate antigen. These mimics are
also called mimotopes. Using mimicry, we
can trick the immune system into targeting
antigens that are otherwise difficult to
target, providing, in principle,
long-lasting immunity.”
Since T cells once
activated carry an immuno “memory” for the
peptide, but do not for the carbohydrate,
the ability to convert carbohydrate
antigen to peptide means the body can
stand guard against that tumor for years
to come. So vaccines can be developed that
were never thought possible to prevent
reoccurrence of tumors.
Additionally, carbohydrate
antigens are much more universal than
protein antigens, meaning
carbohydrate-mimicking peptide vaccines
could treat any number of diseases. “With
these mimotopes, we’re able to elicit an
antibody response and a cellular response
simultaneously,” Kieber-Emmons said. “The
types of carbohydrates we’re looking at
are found in a variety of different cancer
types. We have studies on melanoma; we
have studies in breast cancer; we have
studies in ovarian, prostate, pancreatic
cancers. These antigens are also found on
pathogens like HIV for which we are also
developing mimotopes.”
The new Biacore units allow
Kieber-Emmons to isolate the best possible
binding of carbohydrate antigen to
antibody and then copy those molecular
structures through computer modeling. The
resulting peptide mimics allow scientists
to track down cancer cells that previously
could not be affected through immuno
therapy. “We needed this type of
instrumentation, and in time other people
at UAMS will extend their research to
utilize Biacore,” he said. |