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Holding the Keys to Cancer
CHORI Lab Developing Novel Cancer Vaccine

"Neu is a form of sialic acid, or sugar, that is basically makes itself invisible to all the different ways that we typically have for looking at sialic acids."

CHORI scientists patent new technologies every year that represent potential break-throughs in diagnosis, treatment and cure for many different conditions or diseases. Our Highlight focuses on just one of many promising developments CHORI scientists continue to discover in their ground-breaking bench-to-bedside research.

This month’s highlight features CHORI scientist, Gregory R. Moe, PhD, of the CHORI Centers for Cancer and for Immunobiology & Vaccine Development, whose lab has been pioneering research on a little known and very unique sugar molecule found in cancer cells and other pathogens that could just hold the key to the development of a broadly applicable cancer vaccine, as well as other therapies for cancer.

Dr. Moe and his colleagues discovered the sugar molecule, called de-N-acetyl sialic acid or neuraminic acid (Neu), accidentally, while working on vaccine development for the bacterial pathogen, Neisseria meningitidis group B.

"Neu is a form of sialic acid, or sugar, that is basically makes itself invisible to all the different ways that we typically have for looking at sialic acids," Dr. Moe explains. "The way we found it was one of those things where you start out in one direction and following the data leads to somewhere else that you couldn't have imagined when you started."

Where the Moe lab has wound up is with the characterization of a very special little sugar molecule with a number of different traits that set it apart. Unlike Neu, most forms of sialic acid are found in human cells, and are in fact critical to healthy function.

"Sialic acid is one of the most important carbohydrates in the human body because it is involved in so many different processes critical to cell development," says Dr. Moe. "What makes Neu so interesting is that normal human cells appear not to make it."

This absence of Neu in human cells minimizes the risk that anti-Neu antibodies (antibodies developed to attack Neu) could inadvertently bind with human cells, causing an autoimmune reaction in which healthy human cells are attacked instead. In addition to this key factor, where Neu is found - and in great quantity - is in the cells of a variety of different cancers.

"In every case where we've looked at the normal cells and the corresponding tumor cells, we can't detect any Neu expression in the normal cells," explains Dr. Moe. "For example, some melanoma tumors express a ton of Neu but we do not detect any in normal melanocytes. There really is a significant difference between normal cells and cancer cells, which suggests this may be a very specific way of targeting tumor cells."

Not only is Neu a distinctive feature of cancer cells, Neu also has a unique structure that makes it ideally suited for vaccine development.
"Imagine the sugar as four beads on a chain. In the normal form of the sugar, all of the beads have a negative charge, but in the Neu-containing form, the fourth bead has both a positive and a negative charge."
It turns out that this dual charge serves a very special role. The Moe lab was able to develop anti-Neu antibodies that both recognize, and bind with, Neu by its special fourth 'bead.'

As Dr. Moe explains: "Most of the Neu antigen is inside the cell but when the cell divides large amounts appear on the surface. Antibodies bind with the Neu on the surface of the cancer cells and cause cytotoxic activity - or cell death - against many different cancer cell lines."

This phenomenon, in which antibodies bind to something on the surface of the cell and cause cell death is actually quite unusual. Normally, antibodies bind to antigens on the cell surface but have no effect on processes that affect cell viability.

"What we found is that when you add the antibody, it causes the cells to stop growing at this very early stage of development, which is what makes it so effective," says Dr. Moe. "As a result we're trying to develop therapeutic antibodies that could be used to treat cancers that make this molecule, or to create a vaccine that could elicit antibodies that could target this molecule found in the cancer cells."
Targeting Neu for cancer therapies or vaccines is so promising, in fact, that the Moe lab is already working on development with 2 different biotech companies. Dr. Moe plans on testing the vaccines and therapies in animal models of cancer, with the longer-term goal of being able to establish a safety and efficacy threshold to take it to the final step of clinical trials.

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Tuesday, May 17, 2011 8:19 AM

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