This post is dedicated to the memory of Dr. Richard Grady, whose brave participation in an early CAR T clinical trial is helping to change the treatment paradigm for patients with glioblastoma.
Scientists worldwide are working to develop treatments that harness the power of the immune system to fight cancer. At City of Hope, researchers have found that using CAR T cell therapy, a type of immunotherapy, can be effective in the treatment of glioblastoma — one of the most aggressive brain tumors known to medicine.
A case study published in the Dec. 29 edition of the New England Journal of Medicine outlined the treatment results of a City of Hope patient with glioblastoma. The patient was treated 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.
City of Hope researchers identified a method to effectively target cells that exhibit the IL13Rα2 antigen, which is common in brain cancer. This targeted immunotherapy led to cancer regression that was sustained for 7.5 months after initiation of CAR T cell therapy.
The study was led by neurosurgeon Behnam Badie, M.D., chief of neurosurgery at City of Hope; scientist Christine Brown, Ph.D., Heritage Provider Network Professor in Immunotherapy and associate director of the T Cell Therapeutics Research Laboratory at City of Hope; and Stephen J. Forman, M.D., Francis & Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation and director of City of Hope’s T Cell Immunotherapy Laboratory.
I believe these recent results show we have a potential breakthrough treatment that may have a remarkable impact on patients with malignant brain tumors,” said Badie, co-senior author of the New England Journal of Medicine publication.
Glioblastoma is among the deadliest of human cancers and comes with a devastating prognosis for patients, since current treatment options often have poor outcomes.
“The most exciting thing about our study is that it proves a better treatment may be attainable,” said Brown, the lead author of the report. “We can take a patient who is actively growing advanced, metastatic multifocal glioblastoma, and we can see regression of all lesions, including in the spine. To date, that’s unheard of.”
City of Hope is one of a few cancer centers in the United States offering studies in CAR T cell therapy. It is the only cancer center investigating CAR T cells that target the high-affinity IL-13 receptor (IL13Rα2), 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 into 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 Badie.
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.
City of Hope, with its clinical, research and production facilities all on one campus, is uniquely positioned to lead this work, Brown added. Few institutions are capable of harnessing the same comprehensive “bench to bedside” resources necessary for the discovery, development, manufacturing, quality assurance, testing and deployment of leading-edge treatments.
“City of Hope has accepted the challenge to try to make a therapy that can be used for patients with many different types of cancers,” said Forman. “Our CAR T program here is focused not only on leukemia, lymphoma and myeloma, but also on solid tumors including breast cancer, liver cancer and brain cancer, as a way to try to make effective immunotherapy options for difficult-to-treat cancers.”
For their breakthrough work, Brown and Badie were honored as “game-changing risk takers” by Oprah’s O, The Oprah Magazine and named to that publication’s list of “2017 Health Heroes.”
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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.