Christine Brown, Ph.D.: CAR T Crusader
“I guess my timing was lucky.”
Christine Brown, Ph.D.
, Heritage Provider Network Professor in Immunotherapy, is explaining how, 15 years ago, she happened to join a City of Hope research team that's rewriting the book on brain cancer
— literally one cell at a time.
Luck had little to do with it.
“She's smart. She's fearless. She asked the right questions,” said Michael Barish, Ph.D.
, professor and chair of the Department of Developmental and Stem Cell Biology,
recalling their first meeting. An early mentor, he saw Brown's potential immediately.
“She thinks widely and deeply,” he added. “She willingly entertains out-of-the-box ideas.”
Perfect qualities, you might say, for addressing a uniquely out-of-the-box idea: Extracting a patient's immune cells, engineering them into living, anti-cancer CAR T cells
, multiplying those super-cells by the billions, then injecting them back into the patient.
And watching tumors disappear.
Back in 2002 when I came aboard,” Brown recalled, “CAR T cell therapy was in the early stages of clinical optimization. We didn't know at the time how successful it would be, progressing to where it is today, an actual commercial product that's helping people.”
(Note: the FDA has recently approved two forms of CAR T cell therapy for treating blood cancers.
Brown reflects back on those early days and is amazed at the progress. Along with Stephen J. Forman, M.D.
, Francis & Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation, Brown co-leads the T Cell Therapeutics Research Laboratory
, which to date has treated more than 100 patients in seven clinical trials, with aggressive goals of opening four new clinical studies within the year.
'I Still Get Chills'
Brown knows that extending CAR T cells to solid tumors is going to be particularly challenging, and her research has been focused on developing CAR T cells for the treatment of malignant brain cancers, some of the most lethal and difficult-to-treat solid tumors.
Brown with frequent CAR T collaborator Behnam Badie, M.D.
Working together with a clinical team led by neurosurgeon Behnam Badie, M.D.
, Brown and her fellow researchers are unleashing CAR T cells
on these historically stubborn tumors. The project is still in phase 1 clinical trials but researchers already know it works ... often with breathtaking speed.
“I still get chills when I look at the scans,” Brown said, remembering one case: “21 days and the disease was disappearing!”
More and bigger chills may be coming, courtesy of the California Institute for Regenerative Medicine. CIRM has awarded a $12.8 million grant
to Brown, Badie and their teams to take CAR T cell therapy for brain cancer to the next level. Clearly, CIRM believes in CAR T’s potential and in City of Hope's ability to maximize it.
“City of Hope was the first to try CAR T cells on brain tumors,” said Brown, adding that the decision required a certain “audacity.”
“We were the first to inject those cells directly into the brain, right into the tumor, as opposed to the bloodstream. And now we're the first to introduce CAR T cells into the cerebrospinal fluid (found in the brain's lateral ventricles, the large cavities in each cerebral hemisphere).
“We're looking for the best method and location” to provide maximum benefit and safety.
Their learning curve was aided immensely by the exceptional contributions of one patient, Dr. Richard Grady
, a Seattle pediatric urologist who came to City of Hope in 2015 with recurring brain tumors. The CAR T cell trial was his last hope.
An Inspiring Friendship
It worked, up to a point. Grady lived another 20 months.
“Rich’s response to the CAR T cell therapy was nothing less than remarkable, miraculous even,” wrote Badie shortly after Grady's death. “His glioblastoma had gone into remission and history was made. His largest removed tumor, where the CAR T cells were infused, never returned.
Other tumors, however, away from the CAR T cell infusion site, continued to grow. So Brown and Badie and their colleagues took the steps necessary to receive approval from the Food and Drug Administration to inject the cells into the cerebrospinal fluid, hoping the therapeutic cells would better distribute throughout the brain to target his other tumors. Delivery into the cerebrospinal fluid had never been done before.
After several CAR T cell infusions Rich's disease was eliminated and his life extended. His tumors eventually returned in different parts of his brain, even more aggressively than before. In the end, while we extended his life, we were unable to keep up with the rapid spread of his disease.”
During treatment, Brown developed a deep friendship with Grady and his wife, Dr. Laura Hart.
“On the first day Rich and I met her,” Hart recalled, “I said to myself, 'This is a caring person.' We saw how well-spoken she was, how excited she was about Rich's treatment. We toured her lab. We talked at length about the scientific challenges. And always, she showed such aplomb and graciousness. She's confident, collected, with a kindness and generosity of spirit you don't typically find in basic scientists who never see actual patients.
“She's just a lovely human being.”
A Personal Disease
It simply isn't Brown's style to maintain distance and separation from patients who will benefit from her work. On the contrary, they motivate her.
“Sure, as a scientist I'm shielded a bit,” admitted Brown. “But you know, we do talk about the patients, and when you hear their stories, what they've gone through ... it makes me want to do better.”
It's not her only motivation. Brown personally understands the shock and fear that accompany a cancer diagnosis. In 2012, she was diagnosed with Stage 2 breast cancer.
Now, after treatment, she remains cancer-free. But she remembers.
“It felt so surreal,” she recalled. “I couldn't believe it was happening to me. I was healthy. I'd gone for regular checkups, done all the right things to take care of myself. Nobody in my family had ever had breast cancer. And still. It really drove home the reality that cancer can strike anybody.”
It did more than that.
“Before, I thought of my work as the study of populations with cancer. Not anymore. Cancer is a personal disease that strikes people. People just like me. It's been a defining, life-changing experience for me. And I truly want to make a difference!”
Making a difference — and making it personal — appear to run in the family. Brown's father plays in a charity golf tournament that supports his daughter's work. When Brown's 19-year-old nephew, Nick, lost his grandmother to brain cancer, he organized a fundraising hike of the 2,659-mile Pacific Crest Trail and wrote a $1,500 check to Aunt Christine. “I couldn’t think of a better place to make a donation,” he said.
At home, “Aunt Christine” is married to biotech executive John Desjarlais (“We compete,” she laughed, “in a fun way.”) They have a 13-year-old daughter and 15-year-old son. Brown's downtime generally involves yoga (“keeps me sane”).
Not that there's very much downtime to speak of.
“She's always strategizing for the future,” said Hart, “looking for new ways to replace darkness with light.”
“She is excellent at identifying the critical missing experiments that will complete a story,” added Barish.
And she can't wait to put those missing pieces into play.
“I'm so excited about where we're headed. We're on the cusp of such tremendous potential. Yes, there are plenty of obstacles still out there, but we have so many ideas for overcoming them. We are not out of ideas. Whatever problems remain, I think we're going to solve them.”
Are we talking “cures?”
“Knocking on wood!” she smiled.
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