Interleukin-2 Boosts Cancer Vaccine Effectivene...( dendritic cell finds a T-lymphocyte wi...),Health

dendritic cell finds a T-lymphocyte with a docking site to match the tumor antigen, the T-cell starts producing messenger chemicals which stimulate production of T-lymphocyte "clones." All these new T-cells are equipped with the exact receptor needed to immobilize and destroy one type of cancer.

While the U-M's dendritic cell vaccine alone triggered an immune response against cancer cells, it could not produce antigen-activated T-lymphocytes fast enough to overcome large, well-established tumors, according to Mulé.

"IL-2 gives the immune response a boost," Mulé said. "First, dendritic cells find and activate T-cells with the specific receptors we need to fight the tumor. Then IL-2 induces those T-cells to rapidly divide and proliferate."

The fact that interleukin-2 works at low doses in combination with the U-M cancer vaccine is important, Mulé added, because the toxic effects of high-dose IL-2 therapy have limited its effectiveness against cancer in the past.

"Dosages of IL-2 used in our study were 25 to 50 times lower than the maximum tolerated dosage," Mulé said. "They were comparable to the low dosages used today to stimulate immune response in people with HIV or patients undergoing bone marrow transplantation."

Significant results from the U-M study include:

• Mice injected with three times the lethal dose of tumor (sarcoma) cells and then vaccinated with a sarcoma-specific dendritic cell vaccine showed substantial reduction in tumor size, while mice receiving the same vaccine with IL-2 remained disease free.

• Eighty percent of mice with well-established sarcomas showed complete regression of their tumors after being treated with the U-M vaccine and IL-2.

• Sixty percent of mice whose original sarcomas and breast cancers had spread in their lungs showed no evidence of disease after treatment with the dendritic cell vaccine in combination with interleukin-2. The other 40 percent of mice tr
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Contact: Sally Pobojewski
pobo@umich.edu
734-647-1844
University of Michigan
2-Mar-1999


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