Swimming With Science

From researching and developing therapeutic cancer vaccines to promoting long- distance swimming, W. Martin Kast is persistent in everything he attempts.

by Lori Oliwenstein

 

Martin Kast, Ph.D., knows what it takes to go the distance. As a young man growing up in The Netherlands, he was one of his country’s top long-distance swimmers, setting a national record that still stands today.

He is no less accomplished in his professional life. Kast, who joined the USC/Norris Comprehensive Cancer Center in September 2003, is an internationally renowned cancer vaccine researcher. With the same dogged persistence he applies to traversing wide stretches of water, he is pursuing the development of therapeutic cancer vaccines, as well as an understanding of the basic biology that will allow them to work in the human body.

“Martin Kast is a key addition to our tumor immunology program,” says Zach Hall, Ph.D., Keck School senior associate dean for research. “The use of vaccines is one of the most exciting current areas of biomedical research, and Kast brings us major talent in this area.”

Kast’s persistence in all he attempts is belied by his affable, laid-back personality. He breaks into a wide grin when asked about the brightly colored abstract paintings waiting to be hung in his new office in the Zilkha Neurogenetic Institute. “Those were done by a cousin of mine who I didn’t even know until 10 years ago,” he says with a laugh. “Now I’m helping to represent her work.”

When asked about his research, however, he grows serious, if no less animated. “Usually vaccines work to prevent disease,” Kast begins. “That’s the kind of vaccine everybody knows. But therapeutic cancer vaccines work after the fact. They try to stimulate the immune system to fight off cancer cells that are already in existence in the body.”

Kast’s cancer-vaccine research runs the scientific gamut—from basic inquiries into the biology and pathology of cancer, to translational approaches that look at how to exploit those scientific findings with vaccines, to clinical testing of those vaccines. USC/Norris, he notes, is a perfect place for this type of wide-ranging research. “I’m already collaborating with physicians on campus to test vaccines,” he says, adding that prior to his arrival at the Norris, he had already teamed with Jeffrey Weber, M.D., Ph.D., the Berle and Lucy Adams Chair in Cancer Research and associate professor of medicine, and Laila Muderspach, M.D., assistant professor of obstetrics and gynecology, in a trial of a cervical cancer vaccine that Kast designed.

Now that he has officially joined USC/Norris, Kast says, he can take these collaborations to the next level. “For instance,” he says, “I’m going to be heading up an immune monitoring core facility needed to follow patients in these clinical trials, to see if the vaccine induces the desired responses.” Weber is the principal investigator on a large grant from the Beckman Foundation that will fund this core facility.

Kast’s cervical cancer vaccine uses a viral vector—the so-called Venezuelan equine encephalitis replicon—to deliver mutated human papillomavirus (HPV) genes to a patient. These genes provoke an immune-cell response to the HPV, which is the cause of almost all cervical cancers. According to Kast, more than 99 percent of all cervical tumors have HPV DNA; thus, a vaccine that prompts the immune system to go after HPV should also rev up the immune cells against the tumor.

Kast also is looking into the basics of HPV. He already has identified an HPV receptor, which the virus uses to attach to cells in the body. “We’ve also shown that the virus can target Langerhans cells [immune cells found in the epidermis] and turn them into immunosuppressive cells,” he says. “That might well explain how HPV can hide for a long time in the body without being recognized by the immune system. In other words, we believe we’ve found HPV’s immune escape mechanism. And if we can understand how the virus escapes the immune system, we can then design strategies to block that escape mechanism.”

In addition to his work on cervical cancer vaccines, Kast also is focusing on prostate cancer. “We’ve developed a unique prostate cancer model in mice,” he explains. “And we’ve identified new candidate proteins that could be targeted in prostate cancer in animals—proteins that are similar to those found in prostate cancer in humans. Now we need to work on designing vaccine strategies against those proteins, and see if we can induce an immune response in these mice.”

Kast is also exploring the interplay between hormones and the immune system in prostate cancer. “Male hormones stimulate prostate cancer growth,” Kast says. “That is why some prostate cancers are treated by androgen ablation, where androgen is blocked from acting in the body. As it turns out, androgen ablation also changes the immune system—and we think it changes it for the better.” He and his colleagues are now studying exactly what those changes are, and how they might be amplified, by using their mouse model.

Kast was born and educated in The Netherlands and retains a fervent interest in promoting the language and culture of his home country. In fact, he founded a school for Dutch language and culture during his time at the Cardinal Bernardin Cancer Center at Loyola University in Chicago. It was only the third such school in the United States, Kast notes. And it spawned others of its kind. “About three and a half years ago, I was asked for advice on starting such a school by parents in North Hollywood,” he says. “Now, as it turns out, my two youngest children attend the school, and my oldest is an aide there.”

Kast also has been involved in promoting long-distance swimming in the United States since he first came to this country in 1992. Today, he plays a key role in Swim Across America, a national organization that currently sponsors long-distance swimming races in New York, Boston and Chicago, with funds going to local cancer centers. “Over the last eight years I was involved in organizing a team,” he says. “Every year, I swam a six-mile race in Lake Michigan, and my two daughters swam on the same team with me.”

Now, settled in Southern California, he has his eye on expanding the organization’s scope. “I want to try to organize a race in Los Angeles,” Kast says, “with funds going to USC/Norris.”

Kast says he already feels at home at the Keck School and at USC/Norris, where cancer vaccine research has been underway for some time. “Our goal is to move our knowledge into clinical applications,” Kast says. “And I feel as if this is the place where that will be best able to happen.”