Annual Report 2014

Dr. Stanley Riddell and team

Fred Hutch's Dr. Stanley Riddell (right) and his team members, Tyler Hill (left) and Dr. Daniel Sommermeyer (middle), are pioneering new approaches to battle cancer using killer immune cells – thanks in part to a boost from benefactors Rae and Mark Lembersky. Photo by Bo Jungmayer / Fred Hutch

Catalyzing immunotherapy research at critical stages

Dr. Stanley Riddell's five-year partnership with Rae and Mark Lembersky has brought a promising cancer immunotherapy to the brink of clinical trial

By Dr. Rachel Tompa

Rae and Mark Lembersky met Fred Hutch's Dr. Stanley Riddell at a pivotal point of Riddell's research — he had just identified ROR1, a protein on certain leukemia cells that would later turn out to be a linchpin in a novel immunotherapy approach with the potential to help thousands of patients with many types of cancer.

Riddell and his Fred Hutch colleagues are world leaders in adoptive T-cell therapy, a technique that reprograms killer immune cells to specifically recognize and eliminate cancer cells, sparing healthy cells from the toxic damage of traditional cancer treatments. When the Lemberskys were first introduced to Riddell, his team had made great strides designing T cells loaded with chimeric antigen receptors (CARs), laboratory-engineered proteins that coat the surface of T cells and guide them to malignant cells by homing in on cancer-specific proteins.

The Lemberskys, already long-time supporters of Fred Hutch, connected with Riddell because Mark's aunt had been diagnosed with chronic lymphocytic leukemia (CLL), a blood cancer that afflicts B cells of the immune system. Riddell and his team were developing therapies for CLL and had just found that CLL cells are coated with ROR1 protein in abundance, while healthy mature B cells are not, making it an ideal candidate target for their engineered killer T cells.

"What was scheduled to be a brief meeting turned into a long discussion," Mark said, as he was drawn into the innovation of Riddell's immunotherapy methods and learned about the difficulty the research team faced in garnering traditional funding for their "potentially breakthrough but unproven ideas."

That's where the Lemberskys stepped in. A few weeks after meeting with Riddell, they made a gift that launched the ROR1 project and supported the team's first year of research. With that initial support, the scientists crafted the first CARs specific for ROR1 and conducted preliminary experiments to better understand this potentially life-changing but mysterious protein. Less than a year later, Riddell used that preliminary data to obtain a National Institutes of Health grant to support his ROR1 and other immunotherapy research worth 20 times the Lemberskys' initial investment.

Dr. Stanley Riddell and Alex Salter
Dr. Stanley Riddell, left, and Alex Salter discuss their latest research findings in Riddell’s immunotherapy lab in Fred Hutch’s Clinical Research Division. Photo by Bo Jungmayer / Fred Hutch

Riddell's team was the first to show the promise of ROR1 for T-cell therapy, and in the year following began testing the therapy's safety and cancer-killing power in preclinical models. They also continued their exploration of ROR1's role in cancer and found, to their surprise, that the protein dots the surface of many other types of cancer cells, including mantle cell lymphoma, lung, pancreatic and prostate cancer, and some types of breast and brain cancer.

Riddell and his colleagues were delighted to find that what started as a possible therapy for one type of leukemia might have a much broader reach. Riddell has since led groundbreaking research showing for the first time that T cells bearing ROR1-CARs can eliminate breast cancer and mantle cell lymphoma in the laboratory.

Although Riddell received government support for part of his work, there were other funding gaps along the path from this initial research to clinical trial. Traditional granting agencies simply don't cover every stage of translational research, and that's why Riddell is so thankful for the Lemberskys' continued partnership. For example, a gift from the Lemberskys allowed Riddell to develop a technique to examine ROR1's activity in solid tumors, a technique that is essential to bring the power of ROR1 immunotherapy to cancers beyond leukemia.

"Fortunately for us they continued to catalyze the project at very critical stages," Riddell said. "At every step where we faced a need to generate critical preliminary data to move the project forward, they were there for us."

Now, Riddell and his team are poised to bring ROR1-immunotherapy to patients with a clinical trial that will launch in early 2015. Another gift from the Lemberskys has allowed Riddell to include patients with solid tumors in the trial, in addition to blood cancer patients.

Mark's aunt is still alive and thriving, and although the Lemberskys originally connected with Riddell to find out more about CLL, they are happy their investment has the potential to reach even more people.
"We were very motivated to help Stan’s work that not only might help CLL sufferers but also a broad array of cancer patients. That remains our motivation today," Mark said.

Riddell is grateful for the Lemberskys' financial support — "We would probably never have started with ROR1 if it wasn't for that initial gift," he said — but he also deeply appreciates their engagement with him and his research.

"They really want to know that you're working hard on this, and they want to understand what your obstacles are and how they can help solve them. It's that kind of partnership that really makes it a lot of fun," Riddell said. "The NIH does not take a personal interest, whereas the Lemberskys are as excited as we are at the prospect of making this idea a reality."

The partnership has also been rewarding for the Lemberskys. "Interacting with Stan has been a real pleasure," they said. "Plus, we have been given the opportunity to play a small part in what may well become a major safe and effective treatment for not only CLL, but a number of other cancers as well. What more could donors ask for?"


At Fred Hutch, our sights are set on a cancer-free future. This goal drives us to develop tomorrow's breakthroughs today. By supporting Fred Hutch, you can help propel our lifesaving research. Please give now.



Immunotherapy takes off

Dr. Stanley Riddell's groundbreaking research on ROR1 is just one advance in Fred Hutch's decades-long history of harnessing the immune system to save lives. This year, Fred Hutch's leadership in immunotherapy led to two landmark developments that are opening new doors to cancer cures:

  • In December 2013, Fred Hutch partnered with Memorial Sloan Kettering Cancer Center and Seattle Children's Research Institute to launch Juno Therapeutics Inc. The cancer immunotherapy startup, which raised $310 million in investments its first year, will leverage its impressive array of scientific talent and technology to more rapidly advance promising new treatments to patients.

  • In April 2014, Fred Hutch received its largest donation ever: a $20 million gift from the Bezos family to boost immunotherapy research and extend the successes seen so far in patients with blood cancers to those with lung, colon, breast, pancreatic, ovarian and other solid-tumor cancers.