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New vaccine targets protein associated with mesothelioma, other deadly cancers

Researchers have reduced the size of tumors in lab mice by as much as 80 percent with a new vaccine that targets a rogue protein linked to mesothelioma and other deadly cancers.


The vaccine triggers an immune response that attacks cancer cells that possess a unique carbohydrate structure, while ignoring the healthy cells.


The researchers, from the University of Georgia and the Mayo Clinic in Arizona, engineered tumors in mice that, like human cancer cells, express excessive amounts of MUC1, a protein associated with tumor growth. The MUC1 protein has a 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," said Sandra Gendler, Grohne Professor of Therapeutics for Cancer Research at the Mayo Clinic and co-senior author on the study.


A vaccine directed against MUC1 has tremendous potential, Gendler said. The protein is overexpressed in more than 70 percent of the deadliest cancers, and in 90 percent of so-called triple-negative tumors that are extremely aggressive and difficult to treat.


"In the U.S. alone, there are 35,000 patients diagnosed every year whose tumors are triple-negative," study co-author Geert-Jan 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."


The vaccine, described online this week in the journal Proceedings of the National Academy of Sciences, can also be combined with standard chemotherapy in cancers like mesothelioma that often cannot be treated by surgery.


Caused by asbestos exposure, mesothelioma is an aggressive cancer of the thin membrane that surrounds the lung and other internal organs. The MUC1 protein is typically overexpressed in epithelioid mesothelioma, the most common form of the disease.


MUC1-targeted therapies have been tested on prostate and ovarian malignancies and have shown promise.


The vaccine developed by Boons, Gendler and their colleagues has 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.


The researchers are now testing the vaccine on human cells in the laboratory, and they hope to initiate phase I clinical trials to test the safety of the vaccine by late 2013.


Boons acknowledged that results in the lab often don't mean success in humans. But, he said, vaccines that target the carbohydrate signatures of cancer cells could play an important role in the treatment of the disease.


"We are beginning to have therapies that can teach our immune system to fight what is uniquely found in cancer cells," Boons said. "When combined with early diagnosis, the hope is that one day cancer will become a manageable disease."