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June
13, 2002– (Lexington, Ky.) – Two
University of Kentucky researchers are evaluating a
vaccine to prevent lung cancer recurrences following
primary treatment of the disease.
The Phase I trial is enrolling subjects with diagnosed
non-small-cell lung cancer who already have undergone
treatment with surgery, radiation therapy or chemotherapy. The ultimate goal is to reduce risk of recurrence or
maintain remission following treatment.
Edward A. Hirschowitz, M.D., Assistant professor of
medicine, and John Yannelli, Ph.D., associate professor
of medicine, both in the UK
College of Medicine, are using white blood cells
from patients’ blood to make a vaccine in the laboratory. Then, the vaccine is administered to the patient, causing
the immune system to recognize and destroy residual
tumor cells that can lead to recurrences after cancer
treatment.
Recurrences are not uncommon in lung cancer. In fact,
the outcome of the disease typically is dismal.
“Even following potentially curative surgery individuals
have a 15 to 50 percent chance of tumor recurrence,
depending on the stage of cancer at the time of diagnosis,” Hirschowitz said.
“Because additional medical therapies are not generally
recommended until recurrences are seen, we are using
the window between definitive medical or surgical therapy
and recurrence to enhance the immune response to residual
cancer,” he said.
The vaccine in this study uses dendritic cells, the
most potent immune inducing cells found in the human
body. There are very few dendritic cells in the blood,
but researchers are able to produce more.
“Only in the past five years have scientists learned
to grow these cells in large numbers and manipulate
their biology in laboratory culture. As a result, we
can experimentally culture these cells in the lab and
inject patients with more of these potent cells to engineer
immune responses to different diseases. Just because
a person has cancer, it doesn't mean their immune system
isn't functional,” Yannelli said.
To differentiate into dendritic cells, monocytes, which
are dendritic cell precursors, are removed from a patient’s
blood and stimulated in the laboratory with Granulocyte
Monocyte Colony Stimulating Factor (GM-CSF) and Interleukin-4
(IL-4).
The newly grown dendritic cells are mixed with cancer
proteins derived from lung cancer cell lines. When
the dendritic cells ingest the lung cancer proteins,
these proteins appear on the cell surfaces. Then the
finished cellular vaccines are able to direct the immune
system to target those tumor proteins on cancer cells.
When these cells are delivered to the patient, Yannelli
and Hirschowitz are hoping the cells travel to the lymph
nodes and orchestrate an immune response capable of
finding and killing tumor cells.
The researchers hope to treat 30 patients over a period
of two years. Each patient receives two injections of
the dendritic cells, one month apart. It takes seven
days to make the vaccine. On day eight, it’s injected
into the patient. The second dose is frozen for a month
until the second injection.
Using a person’s immune system to identify and kill
residual tumor cells is not unique to lung cancer. In fact, it is a method that researchers are using to
treat cancers such as breast cancer, colon cancer and
melanoma.
The Kentucky Lung Cancer Tobacco Settlement Foundation
gave the researchers $200,000 to start the project. Later, $500,000 was secured from the Cancer Treatment
Research Foundation.
Kentucky has the highest incidence of lung cancer
in the country. Only one other center in the U.S. is
looking at how the therapy will affect lung cancer.
“For a state that has such a devastating problem,
having the opportunity to do this research here is really
important,” Hirschowitz said.
Even with the advancements of lung cancer treatment
over the past 30 years, the outcome of the disease remains
the same. Hirschowitz and Yannelli hope to affect that
prognosis.
“At this point, we are not looking at cures, but at
prolonging health,” Hirschowitz said.
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