Dance of the T Cells

CAR T-cell therapy, such as SJCAR19, transforms the lowly immune cell into a potential superstar.

 

By Elizabeth Jane Walker; Photos by Ann-Margaret Hedges

 
 

In her imagination, Zoey Smith floats like a dandelion puff across a stage, leaping and pirouetting with other joyful ballerinas. At only 30 pounds, 4-year-old Zoey looks as fragile as spun glass, but she is a mighty little soul.

For the past three years, an aggressive blood cancer has been her unwelcome partner, twirling her around and around and around in a frenzied dance of chemo and relapses.

“Zoey’s had leukemia four times in three years,” says her mom, Whitney Wadkins, “and she’s relapsed four times.”

A new therapy at St. Jude Children’s Research Hospital holds hope for many children who, like Zoey, have cancer that returns or is hard to treat. Known as CAR T-cell therapy, this tactic involves engineering a patient’s disease-fighting T cells to home in on cancer cells and destroy them. Once established in the body, these turbo-charged cancer fighters have the ability to continue their work for years to come.

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.”

Stephen Gottschalk, MD, and Aimee Talleur, MD, talk in the halls at St. Jude

Next steps

Stephen Gottschalk, MD, Bone Marrow Transplantation and Cellular Therapy chair, and his colleague Aimee Talleur, MD, head the SJCAR19 clinical trial.

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.”

Car T Cell Infographic

"CAR T-cell therapy is very powerful. It puts the vast majority of patients who are treated with it into remission."

Aimee Talleur, MD

 

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.”

Crystal Brothers of Ballet Memphis strikes a ballet pose with Zoey Smith looking on.

En pointe

Zoey Smith (pictured with Crystal Brothers of Ballet Memphis). 

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.

“With this immunotherapy approach, we can specifically target only the cancer cells and not other parts of the body. 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.”

Stephen Gottschalk, MD

 

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.”

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