Quest magazine

Using immune cells to fight cancer

Dr. Phil Greenberg turned to research because his patients needed better options. Nearly four decades later, he’s at the forefront of immunotherapy breakthroughs that are delivering new treatments – and new hope.

Greenberg's team re-engineers T cells (shown here in purple), inserting DNA that instructs them to attack cancer cells.

Photo by Photo Quest Ltd.

“Most families didn’t want to talk about failure. They wanted to be hopeful. And I wanted to be hopeful.”

- Dr. Phil Greenberg


Dr. Phil Greenberg spends his days (and nights) focused on research, but the voices of his cancer patients from years ago remain with him.

In his mind he sees a leukemia patient’s parents agonizing over whether to continue treatment or take their child home to die. He sees a woman in her 20s who had run out of options. He remembers how patients grasped at even the small chance a bone marrow transplant would help.

“Most families didn’t want to talk about failure,” he said. “They wanted to be hopeful. And I wanted to be hopeful.”

His wife, Sharon, remembers him weeping for those he couldn’t help. Then Greenberg set out to create better options for patients by devoting his full attention to research – to exploring how the immune system, specifically disease-fighting T cells, could be manipulated to wipe out cancer.

That was why he came to Fred Hutchinson Cancer Research Center in 1976. The bone marrow transplant, pioneered at Fred Hutch, is the first example of the immune system’s power to cure cancer. Transplants eradicate leukemia and other blood cancers not only by replacing diseased bone marrow with healthy donor cells, as originally thought, but also by transferring immune cells that target the disease.

Bone marrow transplants are so effective in part because the donor immune cells more easily recognize any remaining cancer cells as “foreign” – the patient’s own immune system has a hard time distinguishing diseased cells. But the flipside is that transplants often carry nasty side effects such as graft-vs.-host-disease, or GVHD.

Greenberg set out to boost transplants’ power while reducing their toxic effects by fine tuning T cells to zero in on cancerous cells.

“Honestly, when I came here I thought that would be our first project,” he said. “That’s the same project we’re working on now.”

Dr. Phil Greenberg

Dr. Phil Greenberg

Photo by Robert Hood / Fred Hutch

Putting Leukemia Patients Into Remission

In the early ’90s, Greenberg and his team made their first big leap, showing they could tweak transplanted T cells to ward off infection by cytomegalovirus, which is often deadly to transplant patients.

Greenberg’s group is now able to re-engineer T cells’ DNA and his team recently crafted T cells that bind to a protein found on leukemia cells. Although the research is still in early stages, some leukemia patients given transplants that include these engineered cells have gone into prolonged remissions.

“It’s incredibly gratifying to treat a patient and they get better, and when it’s an experimental therapy that you’ve developed – that’s a pretty wonderful thing,” he said.

Advances like these led to December’s launch of Seattle-based Juno Therapeutics Inc. (see Page 3), a biotech company dedicated to accelerating immunotherapy development. It’s a unique partnership between Fred Hutch, New York’s Memorial Sloan-Kettering Cancer Center and Seattle Children’s Research Institute. Greenberg is one of Juno’s founders, as are Fred Hutch’s President and Director Dr. Larry Corey and Dr. Stanley Riddell – whom Greenberg mentored and is now one of the world’s top immunotherapy researchers.

“As a scientist, he is a wonderful blend of being adventuresome and also incredibly rigorous.”

- Dr. Fred Appelbaum

College at 16

At Greenberg’s Long Island, N.Y., high school he had a teacher who “made biology seem the most provocative and exciting thing imaginable,” he said.

At age 16, his parents sent him by bus to college at Washington University in St. Louis where he became a pre-med student. He couldn’t afford a dorm room so he slept in the living room of a frat house, Sharon remembered.

Early in his career, Greenberg struggled to get research funding, just as he sees many young scientists doing now.  “I remember not sleeping,” he said. “I was thinking ‘what am I doing?’”

But he never seriously considered giving up. He loved his work so much that he often brought it home, staying up late into the night. Corey, his longtime colleague and friend, says he often receives emails – and even the occasional phone call – from Greenberg at 3 a.m.

“Phil’s passion for science is infectious,” Corey said.

Greenberg’s best friend, Fred Hutch’s Executive Vice President and Deputy Director Dr. Fred Appelbaum, says when the two of them go skiing, if Greenberg is leading, they never stay on groomed trails.

“Sometimes that leads to seeing something incredible,” Appelbaum said. “And sometimes you find yourself at the edge of a cliff.”

He said that spirit is reflected in Greenberg’s work. “As a scientist, he is a wonderful blend of being adventuresome and also incredibly rigorous.”

As excited as Greenberg is about the recent breakthroughs, he knows even better advances are coming down the pike. The technologies he and his colleagues have developed, he said, will lead to more precise therapies that will treat a broader array of cancers with fewer side effects.

This year, his team will start a clinical trial using immunotherapy to treat lung cancer. His next goal is to use T cells to tackle pancreas cancer.

“This is just the tip of the iceberg,” Greenberg said. “Now we can change T cells to make them function better, make them survive better, make them target the cancer better. The things we’re doing now, we couldn’t even have dreamed about back when I started.”

No tags to display. Taglist will not be shown.