Waldmann Receives Human Immunology Research Award

by Dan Gordon

May 30, 2007

A career that began with a $50 grant from Harvard Medical School has reaped special recognition for Thomas Waldmann from the Dana Foundation and the American Association of Immunologists.

Waldmann, a clinical immunologist at the National Cancer Institute, received the 2007 AAI-Dana Foundation Award in Human Immunology Research May 19 at the immunology association’s 94th annual meeting.

The award was created to recognize excellence in “translational” immunology research— work that has a direct application in human health and disease. Waldmann is the third recipient, following Fred Rosen of Harvard in 2005 and Max Cooper of the University of Alabama at Birmingham in 2006.

“Dr. Waldmann is one of the leaders in the field of human immunology,” said Michele Hogan, AAI executive director. “He has dedicated his life to it.”

A researcher’s path

Applying research in humans was the focus of Waldmann’s career from the beginning.

“From the get-go, it was this interface between basic and clinical (science), long before it was fashionable to talk about translational research,” Waldmann said in an interview before the AAI meeting. “For me, it was always both.”

The $50 grant from Harvard—to study erythropoietin, a hormone involved in the formation of red blood cells—opened a door to the National Institutes of Health (NIH), which appealed to Waldmann because of the prospect of being drafted during the Korean War.

At NIH, he received another lucky break: a co-worker’s departure turned him into a de facto tenured senior investigator, he said. That meant he had his own independent lab with a technician and postdoctoral fellow, and that he could define his own research program.

In addition to continuously thinking about how findings might apply to humans, Waldmann said one of the most important principles throughout his career has been to focus on oddities without trying to explain them away.

“Perhaps the biggest lesson has been to not try to wedge all pieces of information into a prevailing view,” Waldmann said. “Keep an open mind to the possibility that you’re discovering something new. You have to know what leads could be exciting.”

The science

Although Waldmann’s award lecture at the AAI meeting was not geared toward a lay audience, his findings demonstrate the possibilities of applying basic research to treat difficult human diseases: multiple sclerosis, cancer, autoimmune diseases such as rheumatoid arthritis, and human immunodeficiency virus (HIV), to name a few.

His research has shed light on cytokines, which, Waldmann explained before the lecture, are “modest-sized proteins [immune] cells use to communicate.” In one line of research, Waldmann and his colleagues have found a receptor for a cytokine called IL-2.

Daclizumab, a treatment targeting that receptor, has been approved by the U.S. Food and Drug Administration (FDA). The treatment involves something called a monoclonal antibody—“one of the great areas of drug development,” Waldmann said—that lowers the immune system’s rejection of transplants.

The finding applies not just to organ transplants, but also to cell grafts to treat Type 1 diabetes.

The same antibody has led to promising clinical trials to treat multiple sclerosis, Waldmann said, and it might hold promise against a specific (though rare) leukemia that affects the immune system’s T cells.

While Waldmann and his group were researching the IL-2 cytokine, they discovered a new one that could help fight other diseases. This second cytokine, IL-15, is very important in the immune system’s “memory,” which helps prevent recurrences of a disease.

“IL-15 is very, very important for such long-lasting responses in the immune system,” Waldmann said. The cytokine could lead to treatments, and perhaps even vaccines, to fight cancer.

But there is a flip side: too much IL-15 can lead to autoimmune diseases such as celiac disease and rheumatoid arthritis, in which the body’s own immune system acts against it. Researchers are now trying to take advantage of both sides of this coin: boosting the immune response in diseases such as cancer and HIV, but lowering it in autoimmune disease.

Because daclizumab has been approved by the FDA for transplants, it could be tried for other diseases where research is lacking because the principle of immune system suppression might apply. IL-15 is a different story; it has not received FDA approval. However, research on the horizon should clarify its possible uses for diseases including cancer and HIV.

“IL-15 will be in the clinic in 2008,” Waldmann said. “[IL-15 treatments for cancer] work in mice. It truly, truly doesn’t mean they will work in human beings.”

Looking back, looking forward

Amazing progress has occurred in the field of immunology since Waldmann began his career. He is quick to point out that discoveries are helping researchers define what they are up against, even if answers are few.

“You have to realize the change in 50 years,” Waldmann said. For example, “we would not have (had) any idea … about HIV/AIDS 50 years ago, before retroviruses were discovered.”

Hogan said the field of immunology is ripe for more research that will help human patients. Interest in the award is high, she added.

“We’re at a point, I think, in the field where a lot of findings are being translated,” Hogan said. “This is a timely award that honors individuals who are paving the way.”

The nomination process for next year’s award will begin in the fall. Information will be available at www.dana.org and the Web site of the American Association of Immunologists, www.aai.org.