Penn’s CAR-T treatment shrank brain tumors in seven patients, rare progress against deadly glioblastoma

A novel gene therapy pioneered at University of Pennsylvania has shown promise against the deadliest form of brain cancer, according to new studies out this week by researchers at Penn and a separate team at Harvard.

Chimeric antigen receptor T cell, CAR-T, therapy has been hailed as a cure for some types of blood cancer, but researchers have struggled to apply the technique to solid tumors, including brain cancers, which account for the vast majority of cancers.

CAR-T involves removing the body’s T cells — white blood cells that lead the body’s immune response — and genetically modifying them to target cancer when reinfused into the body.

A new, early stage clinical trial at Penn has found that CAR-T treatment reduced the size of glioblastoma, a fast-growing form of brain cancer that can kill within a year. The approach remains far from becoming widely available to patients.

Doctors delivered the treatment by injecting genetically modified white blood cells into the spinal fluid through a port installed in the skull.

Penn’s study involved seven patients, all treated since June 2023. The trial has yet to show if the approach can provide lasting results. Two of the first patients’ tumors began to grow again within months. The third, treated in August, has gone seven months without their tumor growing. Researchers would need to show the treatment can reliably provide at least six months of reprieve in order to be considered significant.

“Our results suggest that this is a step in the right direction,” said Stephen Bagley, an assistant professor of hematology-oncology and neurosurgery at Penn, and the clinical trial’s principal investigator.

Researchers are encouraged by the findings, published Tuesday in the journal Nature Medicine, because they represent a potential treatment for a deadly and difficult to treat brain cancer. There is no cure for glioblastoma and even patients who receive aggressive chemotherapy and radiation treatment typically see their tumors return.

What’s more, the early results show the potential for CAR-T to treat more types of cancer.

CAR-T has “revolutionized how we think about treating patients with cancer,” said Bryan Choi, a neurosurgeon at Mass General Cancer Center, in a statement Tuesday announcing findings of a similar clinical trial. Choi and his colleagues in Boston are also testing whether CAR-T can help treat glioblastoma, and published early results in the New England Journal of Medicine.

» READ MORE: Emily Whitehead was the first child cured of cancer with therapy from Penn. She’s back as a freshman.

More than 20,000 blood cancer patients worldwide, including several hundred in Philadelphia, have been treated with versions of the genetic engineering technique.

Penn cancer scientist Carl June was among the first researchers to discover a way to arm the body’s own immune system against cancer. His team treated their first adult leukemia patients with CAR-T in 2010.

Their first pediatric patient, Emily Whitehead, was cured of a deadly form of leukemia at the Children’s Hospital of Philadelphia.

The Food and Drug Administration last year opened an investigation into reports of a small number of patients who developed new T cell cancers after receiving commercial CAR-T therapies.

» READ MORE: A Penn CAR-T patient later developed new cancer. Researchers are investigating.

But researchers at Penn and elsewhere believe the risk is small, and in the meantime, have pressed forward with research to expand CAR-T’s uses.

Blood cancers are fairly uniform, with one specific protein target. By attacking the one target, CAR-T can effectively eliminate the cancer.

But solid tumors, such as glioblastoma, produce multiple protein targets that can vary from one patient to the next.

Penn’s CAR-T treatment for glioblastoma aims to reduce the size — but not eliminate — the tumor by modifying T cells to attack two protein targets that are most common among glioblastoma.

» READ MORE: After brain cancer surgery, a physician gets an up-close view of rehab and what needs to change | Expert Opinion

Instead of infusing the CAR-T cells into the blood, as is done in blood cancer treatments, they are injected into the spinal fluid, which is constantly washing over the brain.

Doctors install a reservoir port about the size of a quarter in the skull, through which they can inject CAR-T cells directly into spinal fluid.

All patients treated so far in the trial experienced neurotoxicity, which is when brain cells and the nervous system are damaged by a toxic substance, and remain at the hospital for seven days. They experienced confusion, fatigue, muscle aches, and other neurological symptoms that typically subside within 72 hours, Bagley said.

The first two patients saw their tumors begin to grow again within a few months. The third, treated in August, has so far gone seven months without their tumor growing. Still, researchers say it is too soon to say how long-lasting the treatment will be.

Penn expects to enroll at least 18 patients in the current phase of the trial.