Michael Hunter, MD on Medika Life

Breakthrough: New Treatment Sparks Remarkable, Swift Reversal of Brain Cancer in Early Clinical Trials

GLIOBLASTOMA IS AN AGGRESSIVE BRAIN CANCER that forms from star-shaped cells known as astrocytes. It is the most common and most aggressive primary brain tumor in adults.

As an oncologist of three decades, I am still shaken when I hear a patient carries the diagnosis.

I dodged a bullet in 2015 when a large pituitary tumor, likely induced by radiation therapy, turned out not to be a brain cancer.

Photo by National Cancer Institute on Unsplash

I am not talking about the usual pituitary tumor; I have had four surgeries for mine.

I was thrilled to see hints that a new approach offers promise in this context.

The innovative approach led to remarkable responses in three individuals with recurrent glioblastoma. Still, all died within about six months.

Glioblastoma Is A Dreadful Cancer

Before we discuss a possible treatment breakthrough, I want to provide some basics about glioblastoma multiforme.

Glioblastoma multiforme (GBM) is a cancer that starts as a growth of cells in the brain or spinal cord. The malignancy grows quickly and can invade and destroy surrounding healthy tissue.

GBM forms from astrocyte cells that support nerves.

Glioblastoma pre (left) and post (right) resection. https://en.wikipedia.org/wiki/Glioblastoma.

Glioblastoma Demographics

Glioblastoma can happen at any age.

However, it tends to occur more often in older adults and more often in men.

Glioblastoma symptoms include headaches that keep getting worse, nausea and vomiting, blurred or double vision, drowsiness, personality change, and seizures.

Glioblastoma Is Lethal

Treatments might slow cancer growth and reduce symptoms.

There’s no cure for glioblastoma multiforme.

A patient is is receiving radiation therapy. Photo by National Cancer Institute on Unsplash

Despite treatments such as surgery, radiation therapy, chemotherapy, and electromagnetic field therapy, GBM has a poor prognosis.

While treatment can extend the life of someone with glioblastoma multiforme, there is no cure.

Into the Future: Cancer Management

Cancer treatment used to be all about surgery, chemotherapy, and radiation. But now, a whole new world of treatments is making a huge impact.

One type is targeted therapy. These drugs, like Gleevec and Herceptin, go straight for specific changes in cancer cells and kill them. Loads of people with cancer are benefiting from these treatments.

Then there’s immunotherapy, which boosts your immune system to fight cancer.

Some of these drugs have been incredible at shrinking tumors or even making them vanish in people with advanced cancer. And in some lucky cases, these effects can stick around for years.

Micrograph showing a lung cancer (adenocarcinoma) that expresses PD-L1, a target for checkpoint inhibitors. https://en.wikipedia.org/wiki/PD-1_and_PD-L1_inhibitors.

You might have heard of immune checkpoint inhibitors, which are already helping lots of people with cancers like melanoma, lung, breast, and bladder cancer.

But there’s also another kind of immunotherapy called CAR T-cell therapy. It’s not as common as the others, but it’s doing amazing things for tough leukemias and lymphomas, often keeping the cancer at bay for a long time.

How CAR T-cell Therapy Works

CAR T-cell therapy, or chimeric antigen receptor T-cell therapy, is a type of immunotherapy that harnesses the power of the body’s immune system to fight cancer.

Here’s how it works:

Adobe Stock Photos.
  1. Collection of T-cells: First, doctors collect a type of white blood cell called T-cells from the patient’s blood. T-cells are a crucial part of the immune system for identifying and attacking foreign or abnormal cells, including cancer cells.
  2. Genetic Engineering: T-cells are genetically engineered in the laboratory to produce chimeric antigen receptors (CARs) on their surface. These CARs are artificial receptors that empower T-cells to identify and attach to particular proteins, known as antigens, located on the surface of cancer cells.
  3. CAR T-cell expansion: The modified T-cells, now equipped with CARs, are multiplied or expanded to create a larger population of CAR T-cells.
  4. Infusion into the Patient: The CAR T-cells are introduced into the patient’s bloodstream after expansion. Within the body, these modified CAR T-cells actively search for and specifically attach to cancer cells that exhibit the designated antigen.
  5. Attack on Cancer Cells: When a CAR T-cell connects with a cancer cell, it builds a strong immune reaction against the cancer. This reaction can lead to the CAR T-cells directly destroying the cancer cells and calling in other immune cells to help fight against the cancer.
  6. Persistence and Memory: Certain CAR T-cells can remain in the body for long, monitoring for any signs of cancer returning. Memory CAR T-cells can also be produced, swiftly reacting if cancer cells reappear.

Overall, CAR T-cell therapy represents a groundbreaking approach to cancer treatment. It leverages the body’s immune system to target and destroy cancer cells specifically.

The Car T-cell approach offers hope for patients with certain types of advanced or treatment-resistant cancers.

Harvard’s New Study

Massachusetts General Hospital researchers recently took a new approach to CAR-T treatment.

Photo by A n v e s h on Unsplash

MGH researchers engineered CAR-TEAM cells to treat mixed cell populations in tumors.

Collaborating with Mass General neurosurgeons, the team tried the approach in an early (phase 1) clinical trial of patients with recurrent glioblastoma.

Exciting News

Here are the exciting results:

The first three patients in the trial showed dramatic responses within days.

“We were shocked. These results exceeded our expectations,” offered Stephen J. Bagley, MD, MSCE, section chief of neuro-oncology at Penn Medicine.

But did this translate to extraordinary clinical results? In a word, no.

News Headlines Versus Reality

Using a new delivery system and dual-targeting, the novel approach translated to a rapid response.

Coronal (looking front to back) MRI with contrast of a glioblastoma in a 15-year-old male.

Let’s look at the clinic outcomes for the four patients:

  • Patient #1 maintained tumor regression for 33 days.
  • Patient #2 died (not from treatment but from hydrocephalus (for which the patient declined treatment). This patient had two months of stable disease before the hydrocephalus.
  • Patient #3 is at seven months of no progression.
  • Patient #4 had three months of tumor stability.
  • Patients #5 and #6 had one month of stability at the time of the report.

The dual-targeting and a new delivery system produced rapid results.

But There Were Side Effects

All patients had some side effects (neurotoxicity) within 72 hours of treatment.

Photo by Milad Fakurian on Unsplash

Moderate side effects included fatigue, skin ulceration, anorexia, lower oxygen levels, muscle weakness, and drops in some blood counts (lymphocytes, a type of white blood cell).

Into the Future

Researchers are looking to enroll 18 patients in a new trial.

They will examine response length and how that affects survival length.
In addition, the researchers will try to understand why CAR-T works better in some patients than others.

The ability to serially pull out spinal fluid allows for rapid analysis of biomarkers.

My Take

I hope this pilot study improves the management of aggressive brain tumors.

If ongoing studies improve outcomes, researchers may consider using the CAR-T cell approach earlier in the disease process.

Targeting multiple cellular targets with local delivery may help us manage other solid tumors.

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Michael Hunter, MD
Michael Hunter, MD
I received an undergraduate degree from Harvard, a medical degree from Yale, and trained in radiation oncology at the University of Pennsylvania. I practice radiation oncology in the Seattle area.

Michael Hunter, MD

I received an undergraduate degree from Harvard, a medical degree from Yale, and trained in radiation oncology at the University of Pennsylvania. I practice radiation oncology in the Seattle area.

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