Christine Brown, Ph.D., Pioneers Immunotherapy Using CAR T to Target Brain Tumors

August 28, 2018

According to a City of Hope article published in March 2018, Christine Brown, Ph.D., the Heritage Provider Network Professor in Immunotherapy, is pioneering innovation in cancer treatment by “extracting a patient’s immune cells, engineering them into living, anti-cancer CAR T cells, multiplying those supercells by the billions, and then injecting them back into the patient.” The result is watching entire tumors in the brain disappear.

When she first joined City of Hope back in 2002, Dr. Brown recalled that CAR T was just in the early stages of clinical optimization and there was no way to measure its success, how well it was progressing, and its potential to be commercially available. At the time, the Food and Drug Administration (FDA) had recently approved two forms of CAR T cell therapy for treating blood cancers.

Dr. Brown works alongside her colleague, Stephen J. Forman, M.D., the Francis & Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation, to help run the
T Cell Therapeutic Research Laboratory. To date, they have treated more than 100 patients in seven clinical trials, with goals to open four new clinical studies within the year. Along with her team of researchers working with lead neurosurgeon Behnam Badie, M.D., they target malignant brain cancers, which are some of the most difficult solid tumors to treat.

While the project remains in early stages, researchers are confident it works and often does so with miraculous speed. Dr. Brown describes looking at the scans after 21 days and finding that the disease was disappearing. This phenomenal work captured the attention 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.

“City of Hope was the first to try CAR T cells on brain tumors,” said Brown. “We were the first to inject those cells directly into the brain, right into the tumor, as opposed to the bloodstream.” In addition, her team was also 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), searching for the best method and location to safely deliver the cells and maximize its benefit.

In 2015, their research was aided tremendously by one incredible patient, Richard Grady, M.D., a pediatric urologist who came to City of Hope in 2015 with recurring brain tumors with the hope of finding a solution. Dr. Brown formed a special bond with Grady and his wife, Laura Hart, M.D. According to Dr. Badie, Grady’s response to the cell therapy was nothing short of remarkable and when his glioblastoma went into remission, history was made. The largest tumor where CAR T cells were used never returned.

After several CAR T cell infusions Grady’s disease was eliminated, however, tumors that were even more aggressive eventually returned to different parts of his brain. While the team had extended his life, they were unable to keep up with the rapid spread of his disease. The cell therapy worked up to a certain point and Grady lived for another 20 months.

Dr. Brown can personally relate to the fear and uncertainty that comes with a cancer diagnosis. In 2012, she was diagnosed with Stage 2 breast cancer. “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. It really drove home the reality that cancer can strike anybody.” After treatment, Brown remains cancer-free. She describes her journey as a life-changing experience and one that would fuel her passion to make a difference.

Her colleagues describe her as a visionary who is always looking to strategize for the future. She is excellent at identifying the missing pieces to complete the whole story. “I’m so excited about where we’re headed,” said Brown. “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.”

The potential to eventually find a cure for brain tumors is somewhere on the horizon. With the diligence and tenacity of this great team of doctors and researchers, many of us can remain optimistic about the future as we look forward to finally discovering a cure.

Source: CityofHope.org/CityNews, Volume 29. No. 1, Spring 2018

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