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A new study found that CAR T-cell therapy may help people with glioblastoma. Cavan Images/Getty Images
  • Recurrent glioblastoma, the most aggressive form of brain tumor, has no effective treatment.
  • A new form of CAR T therapy, which is currently approved for some forms of blood cancer, could hold promise.
  • In a small study of three patients with glioblastoma, all of them showed rapid and significant tumor shrinkage. However, in two of three patients, the effects were transitory.

A novel form of immunotherapy for recurrent glioblastoma, the most aggressive form of cancerous brain tumor, showed a significant reduction of tumor size in patients who received the infusion.

The results of the research, known as the INCIPIENT Trial, were published this month in The New England Journal of Medicine. Although the effects were significant, they also tended to be transient. The treatment will need to be tested in a much larger group of patients to establish its efficacy.

“To see a response like this in a CAR T trial is really impressive. Not only did the patients do well clinically, but they also had really striking responses on the MRIs. In glioblastoma, if you ever see a tumor shrink, that’s very impressive,” Dr. Ryan Merrell, Division Chief of Neuro-Oncology and an Associate Professor of Neurology at Vanderbilt University Medical Center, told Healthline. He wasn’t affiliated with the research.

In the trial, researchers utilized a next-generation form of CAR T cell, modified immune system cells that are engineered to target cancer, in three patients with glioblastoma.

MRI scanning, a form of brain imaging technology, subsequently showed significant, and in one case near-complete, tumor regression following the infusion. However, only one patient showed durable regression over a sustained period of time. In the other two patients, the results were transient, and the tumors began to regrow.

The study also demonstrated safety and tolerability in all three patients. While some side effects, including fever, fatigue, and encephalopathy, did occur, the treatment was otherwise shown to be safe. The researchers did not establish a “dose-limiting toxicity,” or a dose at which a patient can no longer tolerate the effects of the treatment, indicating that the treatment was generally well received.

“The biggest issue with all of immunotherapy is that you are revving up the immune system to fight the cancer, but you can also get a pretty significant immune attack or immune response in the brain and in the body,” Dr. Gordon Li, Vice Chair and Professor of Neurosurgery at Stanford Medicine, told Healthline. He wasn’t affiliated with the research.

The three participants were all previously diagnosed with glioblastoma due to various symptoms, including headache, confusion, and difficulty reading. All three patients received some form of standard care for glioblastoma, including surgery, chemotherapy, and radiation. Only after doctors discovered a recurrent form of the cancer were they enrolled in the trial.

All three patient’s tumors responded dramatically and rapidly to the CAR T-cell infusion, but the response varied from individual to individual over time.

The first participant, a 74-year-old man, showed “rapid regression” of the tumor a single day after receiving the infusion. However, within two weeks, MRI scans showed that the effects were transient. He received a second dose 37 days after the first infusion. However, the tumor continued to recur, and he subsequently died 63 days after ceasing treatment. The death was not attributed to the CAR T treatment.

Dr. Marcela Maus, MD, PhD, Director of the Cellular Immunotherapy Program at Mass General Hospital and Senior Author of the research, told Healthline that she and her team were in disbelief at the result.

“We were just so surprised to see the tumor looking like it was smaller that we actually didn’t believe it,” she said. “We got another MRI, and that’s not something that you usually do. But, that’s what we ended up doing because we just couldn’t believe it.”

The second participant, a 72-year-old man, again showed significant results. Two days after transfusion, his tumor had shrunk by 18.5%. The tumor continued to shrink as well. Sixty-nine days after a single transfusion, the tumor had shrunk by more than 60%. The response persisted for more than 150 days after the infusion.

Participant three was a 57-year-old woman. Five days after the infusion, the tumor had shrunk nearly completely. However, less than a month after the treatment the tumor showed signs of recurrence.

“Most of the time with standard therapies, you’ll usually see the tumor stabilizing, but to see actual shrinkage or reduction of the tumor is really impressive,” said Merrell.

Chimeric antigen receptor T-cell therapy (CAR T therapy) was originally approved to treat cancers of the blood, such as lymphoma. It is a form of immunotherapy, which utilizes the body’s own immune system to take on cancer cells.

CAR T therapy requires T cells from the immune system that are then genetically engineered to target cancer cells.

However, the CAR T therapy used in this study is a novel, second-generation, form of treatment that identifies two separate antigens — proteins on the surface of cancer cells — to identify and attack with the immune system.

The therapy, known as CARv3-TEAM-E T Cells, targets a molecule known as EGFRv3 and another form known as “wild” EGFR, which are found in glioblastoma. The “TEAM” refers to a “T-cell engaging antibody,” which helps to recruit nearby T cells to fight the cancer.

Put that all together and you have a CAR T therapy that targets glioblastoma-specific cancer cells while simultaneously bringing in additional T cells for support.

“It acts like a little bridging molecule and it brings a T cell in really, close proximity to a tumor cell that expresses EGFR…By having that sort of combo product we’re able to target most of the brain tumor cells in a particular patient,” said Maus.

Despite the findings of the research demonstrating significant shrinkage in tumors and general safety of the therapy. Serious questions remain about the potential of the drug to go mainstream.

Merrell is cautiously optimistic but says it is too early to tell how the therapy would be received in a larger study group.

“You have to be very careful when things like this come out…People will think this is the latest and greatest treatment, when in fact it is unproven and still has a lot of work to be done in terms of determining if it truly is effective or not,” he said.

Meanwhile, Li is more skeptical of the potential of the therapy but acknowledges that the results were significant.

“Any sort of response is a win. In fairness, because we don’t have great therapies,” he said. He notes treatments for glioblastoma have not progressed much in decades.

“There have probably been thousands of glioblastoma clinical trials in the past twenty years. And of those thousands, many have shown responses just like this. And of those thousands of trials, how many have actually led to a phase three trial that led to efficacy? One. And that one has been very controversial,” he said.

Meanwhile, Maus and her team are forging ahead and have already begun the next stage of their trial.

Recurrent glioblastoma, the most aggressive form of cancerous brain tumor, has no effective treatment.

A new generation of CAR T-cell therapy for recurrent glioblastoma succeeded in rapidly and significantly shrinking tumors in three patients. However, the effects tended to be transient.

The novel therapy, known as CARv3-TEAM-E T Cell therapy targets a specific cancer-related protein known as EGFR.

Although promising, the findings of the study are preliminary and must be conducted in a much larger patient population.