Researchers in California used CAR-T therapy, a type of immunotherapy, to treat a Seattle man suffering from recurrent multifocal glioblastoma, according to a case study published in the Dec. 29 edition of the New England Journal of Medicine.
Richard Grady, 50, had been diagnosed with deadly brain cancer that had spread to his spine. He enrolled in a Phase I clinical trial at City of Hope, a Duarte, CA independent research and treatment center for cancer, diabetes and other life-threatening diseases, where had some of his own blood cells removed and genetically modified in the lab to turn them into specialized soldiers to seek and destroy cancer. After failing standard of care therapy of resection, radiation and temozolomide, he developed multifocal disease, with tumors involving both the brain and the spinal cord.
While the type of immunotherapy that Grady received at City of Hope already has helped some people with blood cancers such as leukemia, the way he was given it is new, and may allow its use not just for brain tumors but also other cancers that can spread, such as breast and lung cancers.
Grady was the first person to get the treatment dripped through a tube into a space in the brain where spinal fluid is made, sending it down the path the cancer traveled to his spine. Following the novel treatment, which helped his immune system attack the disease, his tumors completely vanished.
The New England Journal of Medicine case study outlined the results of Grady’s treatment with his own genetically modified chimeric antigen receptor or CAR-T cells, using central memory T cells, a stem cell-like subset of immune cells. He received multiple infusions of the CAR-T cell therapy delivered directly to the brain tumors. Regression was observed for both brain and spinal tumors, as well as increased numbers of immune cells in the cerebrospinal fluid, a clinical response that was sustained for 7.5 months after initiation of CAR-T cell therapy, according to the journal report.
City of Hope is one of a few cancer centers in the United States offering studies in CAR-T cell therapy, and is the only cancer center investigating CAR-T cells targeting the high affinity IL-13 receptor, IL13Rα2, that is overexpressed in a majority of glioblastomas. City of Hope is also administering the therapy locally in the brain, by direct injection to the tumor site and/or through infusion in the ventricular system.
“By injecting the reengineered CAR-T cells directly into the tumor site and the ventricles, where the spinal fluid is made, the treatment could be delivered throughout the patient’s brain and also to the spinal cord where this particular patient had a large metastatic tumor,” said co-senior author of the publication, Behnam Badie, M.D., chief of neurosurgery at City of Hope. “I believe these recent results show we have a potential breakthrough treatment that may have a remarkable impact on patients with malignant brain tumors.”
After three treatments, all tumors had shrunk dramatically. After the 10th treatment, “we saw all the tumors disappear,” and Grady was able to cut back on other medicines and return to work, Badie said.
New tumors, though, have now emerged in different spots in his brain and spine, and he is getting radiation treatment. But his response to immunotherapy lasted more than seven months, and “for him to live more than a year and half” after starting it is amazing for a situation where survival often is measured in weeks, Badie said.
Side effects of the treatment were manageable, including headaches, fatigue and muscle aches, and some may have been due to other medicines Grady needed, doctors reported.
It’s early research, but it’s an advance for the field “that they showed this is safe, at least in this patient,” said Dr. Donald O’Rourke, a neurosurgeon heading a similar study at the University of Pennsylvania. O’Rourke treated 10 brain tumor patients with CAR-T cells but used a single IV dose. A paper detailing results is in the works, but “it’s pretty striking what we’ve found,” he said.
At City of Hope, nine patients have been treated so far, but only three with infusions into the spinal fluid brain cavity. Two of the nine have not responded to treatment, Badie said.
Based on the early successful results seen in the phase I trial for intracranial CAR-T cell therapy, the researchers see enormous potential for a remarkable impact on a wide variety of patients. They remain encouraged that this promising treatment also greatly improves quality of life by preserving patients’ neurological function and minimizing the toxic side effects of other treatments.
The research is being funded through grants from the Gateway for Cancer Research Foundation, the Food and Drug Administration, the California Institute of Regenerative Medicine, and the National Cancer Institute and National Institute of Neurological Disorders and Stroke of the National Institutes of Health. Development of CAR-T cells are made in partnership with Mustang Bio, Inc., a Fortress Biotech Company and a clinical-stage biopharmaceutical company developing novel immunotherapies based on the research of Forman and Brown.
Each year in the United States, about 20,000 people are diagnosed with glioblastoma.
(Sources: Associated Press; Marilynn Marchione, AP Chief Medical Writer; The New England Journal of Medicine; Business Wire)
Filed Under: Drug Discovery