UGA Reports Cancer Breakthrough

From a University of Georgia news release:

Researchers from and the Mayo Clinic in Arizona have developed a vaccine that dramatically reduces tumors in a mouse model. The model mimics 90 percent of human breast and pancreatic cancer cases—including those resistant to common treatments.

The research was described this week in the early edition of the journal Proceedings of the National Academy of Sciences. The vaccine reveals a promising new strategy for treating cancers with the same distinct carbohydrate signature, including ovarian and colorectal cancers.

“This vaccine elicits a very strong immune response,” said study co-senior author Geert-Jan Boons, Franklin Professor of Chemistry and a researcher in the UGA Cancer Center and its Complex Carbohydrate Research Center. “It activates all three components of the immune system to reduce tumor size by an average of 80 percent.”

When cells become cancerous, sugars on their surface proteins undergo changes that distinguish them from healthy cells. Scientists have tried for decades to enable the immune system to recognize those differences, in order to destroy cancer cells and not  normal cells. Because cancer cells originate within the body, the immune system usually doesn’t recognize them as it would foreign cells.

In their research, the scientists used unique mice developed by Sandra Gendler, a cancer researcher at the Mayo Clinic and co-senior author on the study. Just as humans do, the mice develop tumors that overexpress a protein known as MUC1 on the surface of their cells. The tumor-associated MUC1 protein comes with a distinctive, shorter set of carbohydrates that distinguish it from healthy cells.

“This is the first time 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,” Gendler said. “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.”

Gendler said MUC1 is found on more than 70 percent of all cancers that kill. In more than 90 percent of cases, ,any cancers, including breast, pancreatic, ovarian and multiple myeloma, express MUC1 with the shorter carbohydrate.

She explained that when cancer occurs, the cell's architecture changes, and MUC1 is produced at high levels, promoting tumor formation. A vaccine directed against MUC1 has tremendous potential, Gendler said, to prevent recurrence or as a prophylactic in 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.

Boons said MUC1 also is overexpressed in 90 percent of the subset of patients who don't respond to hormonal therapy, such as Tamoxifen or aromatase inhibitors, or to the drug Herceptin. These so-called “triple-negative” tumors are extremely aggressive and difficult to treat, Boons said, 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,” Boons said. “So we might have a therapy for a large group of patients for which there is currently no drug therapy aside from chemotherapy.”

Therapeutic vaccines received renewed attention last year when the Food and Drug Administration approved the first cancer treatment vaccine--Provenge, a drug that treats metastatic prostate cancer. Treatment with Provenge, which is manufactured in Georgia, requires clinicians to isolate immune cells from the patient and send the cells to a lab, where they are linked to a protein that stimulates the immune system. The cells are returned to the patient’s treating physician, who then infuses the drug over three treatments, usually two weeks apart.

Boons’ vaccine is much simpler. Because it's fully synthetic, its components can be manufactured in a lab with assembly-line precision. The vaccine consists of three components—an immune system booster known as an adjuvant, a component that triggers the production of the immune system’s T-helper cells, and a carbohydrate-linked peptide molecule that directs the immune response to cells bearing MUC1 proteins with truncated carbohydrates.

This year Boons founded Athens-based company Viamune to help develop and commercialize the vaccine and the technologies used to create it. The company is one of nearly 30 affiliated with UGA’s BioBusiness Center, an incubator for life sciences start-up companies.

Boons, Gendler and their colleagues are now testing the vaccine’s effectiveness against human cancer cells in culture and are planning to assess its toxicity. If all goes well, they anticipate that by late 2013, phase I clinical trials to test the safety of the vaccine could begin.

The vaccine represents nearly a decade of work for Boons and his team. A 2007 study demonstrated the vaccine’s effectiveness in another mouse model, and Boons is cautiously optimistic about his most recent results. Although promising results in mice often don’t translate to humans, Boons said he is confident that vaccines that target the specific carbohydrate signatures of cancer cells will ultimately play an important role in the treatment of the disease.

The co-first authors on the paper are Vani Lakshminarayanan at the Mayo Clinic in Arizona and Pamela Thompson at UGA. Additional authors include Margreet Wolfert and Therese Buskas at UGA and Judy Bradley, Latha Pathangey, Cathy Madsen and Peter Cohen, M.D. at the Mayo Clinic.

The National Cancer Institute, the Mayo Breast Specialized Program of Research Excellence Grant and the Mayo Pancreas SPORE Grant funded the research.