Researchers at the Mayo Clinic in Arizona and the University of Georgia (UGA) have developed an experimental cancer vaccine that reduced tumors by 80 percent in mice models that mimicked most pancreatic and breast cancers, even those that were resistant to standard treatments.
According to a press release from the Mayo Clinic, the vaccine, described in the journal Proceedings of the National Academy of Sciences, reveals a promising new strategy for treating cancers that share the same distinct carbohydrate signature, including ovarian and colorectal cancers.
When cells become cancerous, the sugars on their surface proteins undergo distinct changes that set them apart from healthy cells, the Clinic explains. For decades, scientists have tried to enable the immune system to recognize those differences to destroy cancer cells rather than normal cells. But since cancer cells originate within the body, the immune system generally doesn’t recognize them as foreign and therefore doesn’t mount an attack.
However, researchers using unique mice developed by the Clinic’s Sandra Gendler, Ph.D., found that like humans, the mice developed tumors that overexpressed a protein known as MUC1 on the surface of their cells. The tumor-associated MUC1 protein is adorned with a distinctive, shorter set of carbohydrates that set it apart from healthy cells.
“This is the first time that a vaccine has been developed that trains the immune system to distinguish and kill cancer cells based on their different sugar structures on proteins such as MUC1,” Dr. Gendler says. “We are especially excited about the fact that MUC1 was recently recognized by the National Cancer Institute as one of the three most important tumor proteins for vaccine development.”
Dr. Gendler says MUC1 is found on more than 70 percent of all cancers that kill. Many cancers, such as breast, pancreatic, ovarian and multiple myeloma, express MUC1 with the shorter carbohydrate on more than 90 percent of cases.
She explains that when cancer occurs, the architecture of the cell changes and MUC1 is produced at high levels, promoting tumor formation. A vaccine directed against MUC1 has tremendous potential to prevent recurrence or as a protection for patients at high risk for particular cancers. A vaccine also can be used together with standard therapy such as chemotherapy in cancers that cannot be cured by surgery, such as pancreatic cancer.
In order for the immune system to recognize MUC1 on the tumor cells, researchers had to develop a special vaccine that had three parts. One part tricks the body into thinking that the cancer cell is a bacterial infection, one part stimulates an antibody response, and one part stimulates a lymphocyte response. If any of the three components were omitted, the vaccine did not work as well.
According to study co-author Geert-Jan Boons, Ph.D., Franklin Professor of Chemistry and a researcher in the UGA Cancer Center and its Complex Carbohydrate Research Center in Athens, MUCI is also overexpressed in 90 percent of the subset of patients who are not responsive to hormonal therapy, such as tamoxifen or aromatase inhibitors, or the drug Herceptin. These so-called triple-negative tumors are extremely aggressive and difficult to treat, Dr. Boons says, and a new treatment option is urgently needed.
“In the U.S. alone, there are 35,000 patients diagnosed every year whose tumors are triple-negative,” Dr. Boons says. “So we might have a therapy for a large group of patients for which there is currently no drug therapy aside from chemotherapy.”
Dr. Gendler and her colleagues are currently testing the vaccine’s effectiveness against human cancer cells in culture and are planning to assess toxicity. If all goes well, phase I clinical trials to test the safety of the vaccine could begin by late 2013.
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