Dance of the T Cells

Immune cells on the move

As you read these words, powerful immune cells in your body are on the move, searching for intruders. If those cells perceive an interloper, they’ll mount an attack. That scenario happens with infections all the time. But here’s the catch: A tumor cell can camouflage itself so the immune system doesn’t recognize it. As a result, the cancer cell is free to reproduce uncontrolled, crowding out healthy cells.

CAR T-cell therapy helps the immune system “see” the tumor cells. Because this kind of treatment reprograms the individual’s own T cells, the dose must be manufactured specifically for each patient.

“You can’t just call the pharmacist and say, ‘Send me immunotherapy,’” says Stephen Gottschalk, MD, chair of St. Jude Bone Marrow Transplantation and Cellular Therapy. “It’s a complex endeavor where we have to collect immune cells from the patient, make them in the laboratory and then infuse them back into the patient.”

Exacting sequence of steps

When doctors believe a child has cancer that will respond to CAR T-cell therapy, their first step is to collect T cells from the patient’s blood. Those cells are then transported to a manufacturing facility. There, scientists add a chimeric antigen receptor (called a CAR) to the surface of each T cell. This receptor will act like a heat-seeking missile to search for a specific protein on the cancer cell’s surface.

Meanwhile, in the hospital, the patient may receive several days of chemotherapy to prepare for the new cells.

Once the engineered cells are infused into the patient, they get to work. The genetically modified T cells roam around in the body. When they discover tumor cells, the T cells multiply and bind to the cancer cells, destroying them.

“CAR T-cell therapy is very powerful,” says Aimee Talleur, MD, of Bone Marrow Transplantation and Cellular Therapy. “It puts the vast majority of patients who are treated with it into remission. To be able to make someone’s own immune system work better is pretty incredible and remarkable.”

A living drug

Unlike chemotherapy, which kills cells indiscriminately, CAR T-cell therapy is a living drug. The cells can replicate for many years, identifying and demolishing cancer cells if a relapse occurs.

“With this immunotherapy approach, we can specifically target only the cancer cells and not other parts of the body,” Gottschalk explains. “We hope to help patients avoid the long-term complications of chemotherapy. We also hope to cure patients who currently cannot be cured with conventional therapies.”

CAR T-cell therapy had its genesis at St. Jude many years ago, when then-faculty member Dario Campana, MD, PhD, and his colleagues found a molecule that helped the immune system attack leukemia cells. The treatment Zoey received was a direct outgrowth of that discovery — the first CAR T-cell therapy to receive FDA approval. Zoey received that version of therapy.

“There’s still a lot to learn about CAR T-cell therapy,” Talleur says, “including how the cells behave once they’re infused into a patient and how this correlates with clinical outcomes.”

Now, St. Jude has developed a new CAR T-cell product for children with leukemia that has returned or has never responded to treatment.

The next generation: SJCAR19

Unlike the therapy Zoey received, the new CAR product is manufactured on the St. Jude campus — in the Children’s GMP, LLC, a facility that manufactures biological products for patient use.

Gottschalk and Talleur are heading the clinical trial, called SJCAR19. St. Jude scientists have made important changes they believe will offer significant improvements over past CAR T-cell therapies.

“Our manufacturing process is a little bit different,” Talleur explains. “We think these cells will last longer in the body than cells from other CAR T-cell therapies. We believe this product will be even safer for patients and will be more effective in killing cancer cells. Through SJCAR19, we also want to answer questions about the patient and caregiver experience.

“Our goal is to improve on existing therapies, and better design and implement future CAR T-cell therapies for a variety of cancer types.”

Gottschalk and Talleur report that other CAR clinical trials are also in the planning stages at St. Jude. These include therapies for children with acute myeloid leukemia, solid tumors or brain tumors.

The dance continues

While doctors and researchers work to create new and more effective CAR T-cell therapies, Zoey continues the important work of a little girl, practicing her ballet moves, coloring pretty pictures and lovingly caring for her little brother.

 “No, you can’t go outside,” she admonishes her dolls. “There are germs. Your ANC is 600, and you’re doing pretty good, but you have to go to clinic next week.”

Zoey’s mom emphasizes that continued CAR T-cell research is crucial.

 “So many children are dying way too early,” Whitney says. “We’ve seen it firsthand. It’s sad to know that parents are losing their children because there are no other options for them.

“It’s super-important to find new advancements to save our children.”

From Promise, Winter, 2019

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