GD2 CAR T cells (NCT04196413)

In the middle of the brain stem there is a bulge called the pons. Everything that keeps you alive without your attention runs through it. Breathing, heart rate, the nerves for swallowing and speaking and moving your eyes.

Diffuse intrinsic pontine glioma grows there. About three hundred children in the United States are diagnosed each year, most of them between five and ten years old. The tumor does not sit in a lump. It grows woven through the pons, so it cannot be taken out, because there is nothing to take out without taking the child's breathing with it. Radiation helps for a while. Half of these children live about eleven months, and fewer than one in a hundred are alive five years later. It is the leading cause of brain cancer death in children.

For decades, nothing added to radiation changed that.

Then a lab at Stanford went looking for a handle. Nearly eight in ten of these tumors carry one tiny change. In histone H three, the spool that DNA winds around, a single amino acid is swapped. That one swap scrambles the instructions that tell a cell which genes to read. And it appears to switch on the enzymes that build a molecule called G D two, a sugar and fat structure that sits on the outside of the cell.

Every tumor sample they tested was covered in it. Healthy brain was not. They had found a flag.

So how do you attack a flag on a cell inside a brain stem? Not with a drug. With a cell.

Take the patient's own T cells, the immune system's hunters. In the lab, give them a new receptor: an outer piece that grips G D two, wired to the machinery that tells a T cell to kill. That is a C A R T cell, a living drug. It takes about a week to make.

The first infusion goes into a vein. Later doses go somewhere unusual, straight into the fluid that bathes the brain, through a small port under the scalp. That port matters twice over, because when the T cells reach the tumor and start working, the swelling arrives in the tightest possible place. The team named the problem and built a routine for it. Watch the pressure, drain fluid through the same port, treat the swelling. So far, in every patient, it has reversed.

Thirteen children and young adults enrolled in the first part of the trial, and eleven were treated. Nine of the eleven improved, in how they felt, on their scans, or both. Four tumors shrank by half or more, and one disappeared. That young man is now more than four years past his diagnosis and still getting infusions. A five-year-old regained the use of her hand and grew two inches. Most of the others, in time, got worse.

Cautious optimism is the phrase the researchers use, and they mean both words. They have since found part of the reason the effect fades. Patients' immune systems learn to attack the engineered receptor itself.

The trial is still open at Stanford, now for ages two to sixty, testing versions designed to last longer. It is led by Michelle Monje. The questions are still safety and dose.

Everything in this film comes from the published record, and it is not medical advice.