Gynecologic oncologist Alessandro D. Santin, M.D., is using the most powerful stimulator cells in the body, discovered in the last decade, to activate the patient’s own immune system to attack the ovarian tumor cells, and only the tumor cells. Dr. Santin calls these antigen-presenting cells, known as dendritic cells, the “sentinels” of the immune system.

Santin, assistant professor of Obstetrics and Gynecology in the UAMS College of Medicine, and a member of the Arkansas Cancer Research Center at UAMS, is the principal investigator on the project, funded for three years with $505,123 from the U.S. Army Medical Research and Material Command. Tim O’Brien, Ph.D., who first cloned CA-125 and TADG-12, the antigens specifically expressed in the tumor, is the co-investigator. In vitro cloning is essential to the process because it produces a bountiful supply of antigen unique to the tumor cells.

“We have evolved in a way that when something bad comes from outside, the dendritic cells can immediately make the immune system aware of it,” Santin said. “But when you have something that grows inside, like a tumor, the dendritic cells in their normal state are not able to activate the immune system properly, and therefore the immune system cannot become aware of the presence of the tumor and destroy it before it gets too big.”

However, dendritic cells can be “loaded” outside the body with small fragments of protein, or antigen, from the tumor cells. Injected into the patient these loaded sentinel cells warn lymphocytes in the blood stream, which then become seek and destroy warriors roaming throughout the lymph system in search of cells with the identical antigen.

 
Alessandro D. Santin, M.D.

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“Because of this important function, you can use them to signal the danger to the body so that they can some way activate the new system,” he said. “And when the system is activated properly, it can kill the tumor. We know that.”

Mortality rates for ovarian cancer are very high because most patients are diagnosed only after the disease is well advanced. Of the 26,000 women who will develop the disease in the United States this year, 16,000 are expected to die.  

In addition, while chemotherapy produces a good response in most patients, it has no answer for chemo-resistant cells that are either left behind or develop after the treatments stop. Santin’s new immunotherapy has shown in the dish to be effective even on chemo-resistant cells, and without the toxicity of chemotherapy or any other side effects.  

The Defense Department grant is to continue research under the microscope, but Santin hopes it can lead quickly to a study to see how effective a vaccination will be on human subjects after the standard course of chemotherapy.

Stefania Bellone, Ph.D., serves as research associate on the project. The research assistant will be Michela Palmieri.

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