Scientists ‘cure’ breast cancer, malaria in mice

Researchers from the University of Georgia and the Mayo Clinic in Arizona (UGA) have developed a vaccine that dramatically reduces tumors in a mouse model that mimics 90 per cent of human breast and pancreatic cancer cases-including those resistant to common treatments.

The vaccine breakthrough, published this week in the early edition of 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.

Also, University of Iowa, United States researchers and colleagues have discovered how malaria manipulates the immune system to allow the parasite to persist in the bloodstream. By rescuing this immune system pathway, the research team was able to cure mice of bloodstream malaria infections.     .

The findings, which was published December 11 in the Advance Online Publication of the journal Nature Immunology, could point the way to a new approach for treating malaria that does not rely on vaccination and is not susceptible to the parasite’s notorious ability to develop drug resistance.         .

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 said: “This vaccine elicits a very strong immune response. It activates all three components of the immune system to reduce tumor size by an average of 80 percent.”

When cells become cancerous, the sugars on their surface proteins undergo distinct changes that set them apart from healthy cells. 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.

The researchers used unique mice developed by Sandra Gendler, Grohne Professor of Therapeutics for Cancer Research at the Mayo Clinic and co-senior author on the study. Like humans, the mice develop tumors that overexpress 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.

Gendler said: “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. 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 pointed out that 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 in more than 90 percent of cases.        .

She explained 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, Gendler said, as a preventative for 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.

UI postdoctoral research scholar and lead study author, Dr. Noah Butler, said: “Malaria is chronic, prolonged infection and the host immune defense has a tough time clearing it and sometimes it never clears it. We’ve determined that this prolonged infection actually drives dysfunction of the immune cells that are supposed to be fighting the infection, which in essence allows further persistence of the parasite infection.”

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Courtesy University of Georgia, via Biomechanism

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