11:21am Tuesday 22 August 2017

Fighting Cancer One Molecule at a Time

But while building molecules may be as much fun as building a LEGO tower, it also serves a higher purpose. In the case of Laura Kiessling, one of those purposes is to fight human cancer cells; another is to learn how we may someday prevent cancer altogether, much like we learned decades ago how to prevent children from coming down with measles, mumps or rubella.

“We have known how to make vaccines for a long time, but all the low-hanging fruit is kind of done,” Kiessling says. “The strategies of the past just don’t work for cancer. To me, carbohydrates have the potential to help us understand what it would take to make a new kind of cancer vaccine.”

Kiessling is a Steenbock Professor of Chemistry, a Laurens Anderson Professor of Biochemistry, and a UW Carbone Cancer Center-affiliated researcher. Ever since she joined the University of Wisconsin–Madison some 25 years ago, she has put all her eggs in one basket: carbohydrates, a group of molecules made up of carbon, hydrogen and oxygen atoms, have been the focus of her lab from day one.

The specific carbohydrates Kiessling studies are those that cover every known cell on the planet. These surface carbohydrates have been conserved through evolutionary history, but their exact role has only recently begun to be understood.

“The carbohydrate coat defines a cell’s identity: it is like a face that makes the cell recognizable by other cells,” Kiessling explains. “But it also reports on the cell’s current state: a cancer cell puts different carbohydrates on its surface than a normal cell, which is why they are often used as tumor markers.”

For Kiessling, the world of carbohydrates is fascinating because it’s full of surprises. Her recently published research on a human protein called intelectin is a prime example.

“First, we were surprised to find that this human protein does not recognize any known human carbohydrates, but is exquisitely sensitive to microbes,” Kiessling explains. “The next surprise came when we showed that it binds to many different microbial sugars; in other words, it is not at all specific to any particular type of microbe.”

Kiessling, marveling at this example of “incredibly cool evolution in action,” says her research team was stunned that a protein could have that ability. Going forward, the team hopes to figure out why this protein, which is likely part of our natural defense against microbes, is also upregulated in cancer patients.

Once the researchers illuminate the exact mechanism that makes our immune system so powerful in fighting microbes, they hope to ramp up that same mechanism to better fight cancer, and perhaps, down the road, to prevent it from taking hold in our body with a newly designed cancer vaccine.

Another type of immunotherapy involves “decorating” existing human cancer cells with a microbial carbohydrate. Using cell lines in a culture dish, Kiessling has already demonstrated that this strategy of making cancer cells look like microbes enables naturally occurring human antibodies to eliminate only the tumor cells, while leaving nearby healthy cells intact.

“I am convinced that the combination of advances on the chemistry side and advances in our understanding of the immune response will pave the way for new frontiers in using our own immune system to target cancer,” Kiessling says. “I think that’s really exciting.”

 University of Wisconsin School of Medicine and Public Health


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