Summer 2010

Just call him Dr. T-cell

Dr. Phil Greenberg’s pivotal T-cell research has energized the emerging field of immunotherapy

By Anne Broache

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In many ways, defeating cancer is like assembling an exceedingly tricky jigsaw puzzle. We may have some ideas about the big picture and the contours, but we’re left with a daunting jumble of interior pieces to match up, little by little.

Fortunately, Dr. Phil Greenberg likes puzzles. "I like the idea of asking a question and finding an answer,” he said, his trace Brooklyn accent exuding enthusiasm and his eyes twinkling behind wire-rimmed glasses.

Dr. Phil Greenberg
Dr. Phil Greenberg
Greenberg and his colleagues focus their attention on one major portion of this puzzle: the function of rare disease-fighting immune cells called T-cells. During his more than three decades of research at the Hutchinson Center, he has become a world expert in discovering how T-cells can be manipulated to treat a range of cancers.

T-cell therapy is one piece of a broader effort to revolutionize treatment of cancer and other diseases by empowering the human immune system to wipe out illnesses. This approach, known as immunotherapy, offers the promise of cancer care that is less toxic and less invasive to the patient, while yielding better success rates than conventional treatments. Today, Greenberg is one of more than 30 researchers who participate in the Center’s internationally renowned immunotherapy research program.

Greenberg, who serves as head of the Center’s immunology program and is professor of immunology and oncology at the UW School of Medicine, was part of a team in the early 1990s that first showed it’s possible to extract T-cells from a sick patient’s body, multiply them to the billions in the laboratory, and infuse them back into the patient to seek and destroy particular diseased cells.

This initial success, backed by many years of testing in model organisms, involved protecting immune-compromised patients from cytomegalovirus infection, an often-deadly complication common to people who have received bone marrow transplants. Since then, Greenberg and his colleagues have found that the same approach—known as adoptive T-cell therapy—can cure late-stage melanoma, a deadly form of skin cancer.

 

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Dr. Cassian Yee, who started out in Greenberg’s lab, continues to refine this therapy in his own laboratory. This technique has also shown potential to treat other cancers, including prostate and pancreatic cancers, and aggressive leukemias, Greenberg’s primary mission at the moment.

Despite this promise, T-cell therapy is still in its infancy. It remains a challenge, for instance, to identify precisely which of the thousands of components of a cancer cell both make it malignant and could actually be exploited—the Achilles’ heel, if you will—by deploying an army of T-cells appropriately matched for the task.

To that end, Greenberg and his lab recently discovered a protein that appears to be a hallmark of certain leukemia cells. With that knowledge, they have developed a way to engineer genetically modified T-cells that are, in a sense, supercharged. They’re not only more adept at seeking out and destroying leukemic cells but also can be multiplied in the lab—and thus delivered to a patient—much more rapidly than current approaches allow.

“Within two weeks we can create billions of T-cells that are better than the original ones,” Greenberg said, whereas current T-cells take months to clone and cannot be effectively generated for all patients. Greenberg and his colleagues plan to begin clinical trials soon for this promising new technique in acute leukemia patients whose cancer has relapsed. They’re also working to develop similar strategies to fight prostate and pancreatic cancers. In addition, they’re collaborating with a large team to develop more effective laboratory models for investigating vaccines that bolster the immune system’s response against HIV.

Greenberg first began pondering how the immune system could be used to fight cancer and disease after medical school. By 1976, Greenberg had joined the faculty of the then-young Hutchinson Center, which attracted him because of its rare combination of expertise in both cancers and the science of the immune system. Back then, medical luminaries like Dr. E. Donnall Thomas were in the early days of developing bone marrow transplantation, which has now provided critical clues about the immune system’s potential to fend off cancer and given rise to immunotherapy.

A self-described “people person,” Greenberg split his time between seeing cancer patients and conducting research until making the difficult decision in the mid-1990s to devote his attention to his ever-expanding laboratory activities.

“Being a physician and taking care of patients is a very special opportunity,” he said. “You get a gratification that you can get from nothing else in your life. When I gave that up, I felt a substantive loss.”

Still, Greenberg finds peace in knowing that he is working “to develop something that will ultimately help patients and be a unique contribution.”

And he’s truly committed to the effort, right down to the car he drives: His license plate reads, “DRTCELL.”


How you can help: During the next five years, the Hutchinson Center needs $28.5 million to advance and broaden the field of immunotherapy. To donate, visit www.fhcrc.org/immunotherapy or call 206-667-4399 or 800-279-1618.
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