He'd spent 12 hours on his feet surgically removing three aggressive brain tumors from three different patients — but he wasn’t ready to slow down.
Badie, chief of neurosurgery and director of the Brain Tumor Program at City of Hope, went from the operating room back to his office to review scans of a patient who was enrolled in a promising clinical trial for which he is a principal investigator. He and his colleagues are studying the potential of CAR T cell therapy as a way to treat glioblastoma, an aggressive and fast-growing type of brain tumor.
Beyond the Operating Room
Glioblastoma, Badie said, is one of medicine’s most heartbreaking diseases. The average lifespan for someone who has been diagnosed with glioblastoma is often measured in months, not years. Not much progress has been made on the treatment of the disease over the past two decades.
While about 25 percent of brain tumors are malignant (cancerous), nearly 60 percent of Badie’s patients have a malignant brain tumor.
“No matter how well the surgery goes, how skillful you are as a neurosurgeon, malignant tumors still come back right at the surgical area,” said Badie. “It is always difficult to go to patients and tell them their surgery was successful, but there's a good chance the tumor will recur in a few months.”
Driven in part by the plight of his patients, Badie spends nearly as much time in the laboratory as he does in the operating room. He wants to help not just today's patients, but tomorrow's.
“I’ve realized being a neurosurgeon is not enough,” said Badie. “The only way to truly beat this awful disease is through science and technology. And that’s one of the reasons I came to City of Hope.”
A Defining Moment
Ten years into his career as a neurosurgeon, Badie’s world was turned upside down when he learned his father, the family patriarch, had a malignant brain tumor.
“I remember seeing his brain MRI and I knew right away what was going to happen to him,” said Badie. “It was a turning point in my life.”
Badie’s father lived for almost a year after the initial diagnosis. And looking back, Badie finds it ironic that it was his dad who actually encouraged him to go into medicine.
“Before that I was a mere surgeon,” said Badie. “I’d done thousands of brain surgeries and many of them were the same. But after that experience, I saw the other side of having a brain tumor. I saw the family’s side. My dad gave me a better understanding of what the families and the patients go through; the sense of desperation and urgency – I think that really completed me as a neurosurgeon. It has motivated me to do more than just surgery.”
Badie is now working to transform brain tumor treatment using nanoparticles, engineered T cells, engineered stem cells and other novel treatments. But he has seen the most encouraging results with CAR T cells.
Advancing the Technology to Fight Brain Tumors
As Badie sits at his desk, pulling up scans of patients in his CAR T cell therapy clinical trial, he thinks back to the day he first realized that the research he had been working on for nearly 10 years was starting to bear fruit.
“I still remember that evening when I first saw the scans of one of our first patients,” he recalled. “I was sitting in my office and for the first time I had that feeling – something we’d been working on for a decade suddenly showed some promise.”
The clinical trial he was referring to involves a specific kind of immunotherapy known as chimeric antigen receptor (CAR) T cell therapy. This type of treatment trains a patient’s own immune system to kill cancer cells.
This first-in-human phase 1 trial uses a patient’s own modified T cells to fight their tumors. It’s designed to target the tumor head-on by delivering the modified cells directly to the tumor site.
City of Hope is one of only a few cancer centers in the United States offering human studies in CAR T cell therapy. It is the only cancer center investigating CAR T cells administered directly to brain tumors.
Those scans Badie recalls so vividly showed a patient’s brain and spinal tumors shrinking – nearly disappearing – after Badie injected the CAR T cells into his ventricular system, where the spinal fluid is made.
This patient had already gone through standard treatment and, like most patients diagnosed with glioblastoma, his tumors returned shortly after treatment. The patient was told he had no options left before finding Badie’s trial.
The experimental procedure had never been tried before and Badie, who has been helping patients battle brain cancer for 20 years, had never seen results like these.
“I clicked on the images and I thought, ‘No, this is probably the wrong patient,’” said Badie. “Then I went back and clicked on the MRI images again and I realized that yes, this was the right patient. His tumors just weren’t there anymore.”
After calling the patient’s wife to deliver the news, Badie immediately called scientist Christine Brown, Ph.D., his co-principal investigator.
“I remember the day absolutely clearly,” said Brown, the Heritage Provider Network Professor in Immunotherapy at City of Hope. “Dr. Badie called me, it was November 30th and he said, ‘Christine. You will never believe it. All his tumors are melting away.’”
Behnam Badie, M.D. and Christine Brown, Ph.D.
What It Means for the Future
What Badie and his team have achieved may be just the beginning.
“Treating brain tumors is very challenging,” said Badie. “There are many limitations and obstacles. They are very invasive, so it’s hard to remove the entire tumor without damaging the brain. And getting drugs into the brain has always been a major challenge because the blood-brain barrier, a natural defense system, keeps many drugs out.”
City of Hope researchers see enormous potential for CAR T therapy. They remain encouraged that the treatment greatly improves quality of life by preserving patients’ neurological function and minimizing the toxic side effects of other treatments.
“We still have a lot of work to do, but just having that positive result from the low dose of the CAR T cells is really, really promising,” said Badie. “Demonstrating that this technology works in a handful of patients gives us hope that CAR T cell therapy will change the way we treat brain tumors.”
A treatment like this is something Badie wishes he’d had for his father.
“It's very common for patients to ask me, 'What would you do if it this was you or your family?' And I tell them I've been there with my father. He had the same cancer 11 years ago and I wish I had this option for him at that time — but I didn't.
“There's no question in my mind that what we're doing now will impact a lot of lives.”
City of Hope clinicians and researchers are brimming with optimism as 2020 begins. Cancer care is changing rapidly, and the pace of change is accelerating. In 2020 look for major advances in gene-based therapy, immunotherapy and many other areas.
City of Hope has opened a first-in-human clinical trial for patients with recurrent glioblastoma – the trial is the first to combine City of Hope’s unique CAR T cell therapy with immune checkpoint inhibitors.
Diagnosed with a rare, fast-growing blood cancer and ineligible for a lifesaving stem cell transplant after failing chemotherapy, treatment with a breakthrough CAR T drug called Yescarta was Caitlin Buchanan's best hope for survival.