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UK MARKEY CANCER CENTER RESEARCHERS DEVELOP LUNG CANCER VACCINE

By Tammy Gay

 

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“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.”

Edward A. Hirschowitz, M.D., assistant professor of medicine in the UK College of Medicine

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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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