Developing New Immune-Based Therapies for Blood Cancer
Brian Till, Lymphoma Physician-Scientist
One to two days a week Dr. Brian Till heads out from his lab at Fred Hutchinson Cancer Center into the clinic to see patients with lymphoma and other blood cancers.
Some have slow-growing but tenacious disease, and he cares for them as they go in and out of remission through a series of treatments and clinical trials over many years. Others have forms of the disease that grow quickly but that he can nevertheless usually cure in months with grueling — but effective — therapies.
Few of them know that he was once in their place.
As a college freshman in Washington, D.C., Till developed night sweats, enlarged lymph nodes, and other concerning symptoms. They were initially dismissed by his doctor when he returned home to Arizona, but the staff at the student health center were concerned enough to follow up.
Soon, Till learned he had Hodgkin lymphoma. He took a year off from school to undergo rounds of chemotherapy and radiation. Then, he went back and finished his degree.
“I was cured of my lymphoma, and that whole experience just sort of blew my mind,” Till said. “I thought, ‘wow, you can actually cure cancer with medicine injected in your arm.’ And I wanted to get in on that.”
The vague sense he’d had up until that point of wanting to become a doctor then came into sharper focus. During his subsequent medical training, he felt a pull to oncology. That draw came in part out of his own experiences, but also because of the special, intimate relationships he saw between cancer doctors and their patients as they travelled together through some of the darkest days of the patient’s life – and, especially, when there was the hope of a cure at the end of that journey.
“There are a lot of great people out there that you get the privilege to know for a long time. You don’t know everything about their lives, but this is a pretty big part of their life that you’re involved with,” he said. “And especially when things go well, it’s pretty rewarding to see them thriving because of a treatment that you gave them.”
But things don’t always go well, and some lymphomas turn out to be resistant to treatment. While many standard and experimental treatments are available that can sometimes help people with these particularly difficult lymphomas live for years with their cancers, eventually that long list of options can come to an end.
“What I often will say to the family members if their loved one dies from lymphoma — in addition to expressing my condolences — is, ‘I wish we had more to offer. I wish we could have done more,’” he said. “This humbles us. This experience is so humbling and shows us that even though we can cure some of our cancers, we still have a lot of room for improvement.”
And that’s where his research comes in.
In his laboratory, Till develops new forms of treatments that harness patients’ immune systems to fight their non-Hodgkin lymphomas. He has focused so far on a molecule called CD20 that is found on the surface of many lymphoma cells. Drugs that kill cells bearing CD20 are a longtime cornerstone of lymphoma treatment. Under the leadership of his former mentor at the Hutch, the late physician-scientist Dr. Oliver Press, Till played a key role in several firsts in the development of a newer type of immune therapy for CD20-positive lymphomas, called CAR T-cell therapy.
In this strategy, a patient’s own T cells — a type of white blood cell — are genetically engineered in the laboratory to arm them with a molecule called a chimeric antigen receptor, or CAR, that allows them to recognize and destroy cells with CD20. After the cells are modified and multiplied, they’re put back in the patient to kill their cancers.
“This experience is so humbling and shows us that even though we can cure some of our cancers, we still have a lot of room for improvement.”
Till helped to lead the first published trial of a CAR T-cell therapy for lymphoma, and, subsequently, led the first-published trial of a so-called third-generation CAR T-cell therapy for this cancer, which improved on the previous CAR molecule’s design. These trials demonstrated the safety, feasibility and promise of this type of strategy for lymphoma.
After years of work in the lab, Till improved many more aspects of his team’s particular experimental CAR-T therapy, from the design of the CAR molecule to their method for genetically modifying the T cells. The result was that the Hutch licensed this CAR to a biotech company to be tested in clinical trials and, potentially, developed into a commercial product.
“To see something that came from my lab put a patient with bad lymphoma into remission — it’s super gratifying to see that,” he said.
Researchers need to study patients in clinical trials for a long time to learn how long remissions are going to last. But Till optimistically hopes that some who are treated with products he helped to develop might be cured, as he was years ago. Even so, there are always going to be patients for whom any promising new treatment doesn’t work well enough. And some of them will be people he’s known and cared for over many years.
So, he hopes that, for the sake of these patients and those to come, that any new treatment he develops in the future helps save lives — but that research in his lab and others around the world keep racing forward to find even better options.
“Even if this treatment ends up being a successful FDA-approved treatment someday, something else will come along and knock it off its pedestal,” he said, “which is good for patients.”
— Updated October 5, 2023
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