Dual targeted cell therapy offers hope in treatment of brain cancer
CANCER DIGEST – March 16, 2024 – Using CAR T cell therapy that targets two proteins associated with the most common and most aggressive type of brain cancer, called glioblastoma, appears to produce early and sustained tumor shrinkage, results of an early phase I clinical trial show.
The clinical trial aimed at demonstrating safety involved six patients with recurrent glioblastoma (GBM), a fatal form of brain cancer in adults. Most such patients survive an average of less than a year. The early results of this trial were reported in the March 13, 2024 Nature Medicine.
CAR T cell therapy, which has shown success in blood cancers such as leukemias and lymphomas has not been as effective in solid tumors. The therapy involves removing immune cells that recognize a specific antigen, or protein produced by the cancer from the patient, engineering them to more specifically target that antigen, and growing billions of them in the laboratory and then re-infusing them back into the patient. The goal is to give the immune system the needed boost in numbers to overwhelm the cancer.
The trouble with solid tumors such as glioblastoma is that the cancer cells are not all the same and therefore produce multiple antigens that the immune system needs to recognize. The researchers at Penn Medicine’s Abramson Cancer Center decided to develop a CAR T cell therapy that targets two of the most common antigens produced by glioblastoma tumors.
"This is the first time CAR T cell therapy with two targets, rather than just one, has been administered to patients with glioblastoma," Stephen Bagley, MD, MSCE, lead investigator said in a press release. "Our results suggest that this is a step in the right direction, and this method, when delivered through the patient’s spinal fluid, could be the key to developing therapies that outsmart the complicated defense systems of GBM."
In this trial six patients received the dual-targeted CAR T cells through an injection into the spinal fluid in order to get the cells into the brain more directly than through the blood. MRI imaging of all six patients 24 to 48 hours after the injections showed immediate response with reductions in tumor size in all six. So far the tumor reductions have been sustained for several months.
While that response is encouraging, the researchers noted that none of the responses met the criteria for an objective radiological response, meaning the tumors did not completely disappear.
In addition all patients experienced neurotoxicity, meaning the CAR T cells harmed neurons in the brain, resulting in generalized muscle weakness and fatigue. One patient experienced grade 3 anorexia or loss of appetite. All were successfully treated for their neurotoxicity with dexamethasone, an anti-inflammatory drug.
The researchers concluded their journal report stating that while the results are encouraging, the approach needs confirmation with more patients and longer follow-up.
Sources: Penn Medicine press release and Nature Medicine
