CAR T-cell therapy offers an approach to treating pediatric cancer that’s effective and has fewer side effects than many of the therapies currently regarded as the standard-of-care. At UVA Health Children’s, Daniel Lee, MD, and Michael Engel, MD, from pediatric oncology/hematology have been early advocates of these cancer treatments that leverage the immune system.
In 2017, UVA Health Children’s first pediatric CAR T patient, a teenager, received this lifesaving treatment. Since then, more children have received CAR T-cell therapy, including 6 at UVA Health Children’s. In the region, UVA Health Children’s is the only program to offer both FDA-approved CAR T-cell therapy and other versions available via clinical trials. And the list of cancers that CAR T has shown success with continues to expand.
“We are only just getting started with opportunities that CAR T-cell therapy offers for treating cancer,” says Lee. “There are so many things that will soon be available for treating pediatric and adult cancers with these new tools.”
One recent CAR T-Cell patient is Jillian. A 13-year-old girl whose relapsed leukemia was treated with CAR T-cells in December 2023.
Caring for Jillian with CAR T-Cell Therapy
In September 2019, Jillian, then only 9 years old, was admitted to UVA Health Children’s for GI symptoms and a low white blood cell count. Eventually, her symptoms led to a diagnosis of pre-B cell acute lymphoblastic leukemia (ALL). ALL is the most common form of childhood leukemia and represents approximately 30% of all childhood cancers. She was treated with conventional, front-line chemotherapy by Engel and went into remission. The vast majority — up to 90% — of children diagnosed with ALL will go into remission with standard chemotherapy.
But, unfortunately, Jillian relapsed in September 2023. A new approach was needed. At that point, Jillian’s care team, including Engel and Lee, recommended CAR T-cell therapy. But CAR T takes time.
“This treatment is not something you just pull off the shelf,” says Lee. “It’s a cell-based immunotherapy product. You have to collect T-cells from patients and go through a manufacturing process to insert the appropriate receptor into the patient’s T-cells. The process takes a minimum of 3 weeks.”
To keep the process as short as possible, UVA Health Children’s is able to produce custom CAR T-cells at its own on-site Good Manufacturing Process (GMP) production facility. This infrastructure can help improve turnaround time for CAR T-cell production and allow for a clean production process.
Restarting Chemotherapy
While waiting for CAR T-cell therapy, Jillian received re-induction chemotherapy to keep her leukemia under control.
Chemotherapy plays an important role in preparing for CAR T. It keeps the disease from advancing while the therapy is prepared. But it also permits a small amount of leukemia to remain. So when the CAR T-cells are infused they destroy residual leukemia cells. Then they remain vigilant to kill any that initially escape the therapy.
By December, Engel and Lee had Jillian’s new T cells, and since she hadn’t gone into remission, it was time for her therapy.
Building on Success of CAR T-Cell Therapy
“With CAR T, therapy can potentially be one-and-done. While early, long-term side effects from CAR T-cell therapy seem far less severe than those we see with chemotherapy and radiation. The beauty of CAR T is the way it works to recognize molecules on the outside of cancer cells,” says Engel.
When patients are diagnosed with leukemia, like Jillian, they don’t just have a single version, called a clone, of the disease. From a molecular perspective, treatment resistant sub-clones can hide in a sea of disease that is more susceptible to front-line chemotherapy. This can mean that a patient who appears to be in remission can still have undetected sub-clones that become the source of recurrent disease.
“For Jillian’s relapsed leukemia, even being resistant to conventional chemotherapy, CAR T cells can be effective as long as the leukemia cells continue to express the target of the CAR T-cells (CD19) on their surface. CAR T-cells don’t care about the underlying genetics of the leukemia. As long as CD19 expression is retained on the surface of the leukemia, the CAR T-cells swoop in and kill that cancer cell. That’s where CAR T offers a difference compared to conventional chemotherapy approaches we’ve used to treat cancer for decades. They're like smart bombs. They kill cancer cells with little collateral damage. This targeted approach is a game changer. It will increasingly be a part of therapy for all kinds of cancers.”
While the goal is for CAR T-cell therapy to become an outpatient procedure, Jillian’s care team performed her infusion in the hospital. For 2 weeks, they continued to monitor her from within the hospital. This precaution is to help manage any toxicity from the CAR T-cells.
Making CAR T Safer
Much of Lee’s research is focused on reducing CAR T toxicity, especially for children who have a lot of disease. That’s because when CAR Ts become active, they secrete massive amounts of cytokines as part of the immune response.
This reaction can cause side effects like high fevers, difficulty breathing, low blood pressure, and neurotoxicity. While these side effects are generally self-limited, they can be dangerous and require a center that can manage them concurrently.
Lee is a global expert in the unique toxicities from CAR T-cell therapies and is working to engineer these products to be more safely administered. Bringing in experts like Lee is one way that UVA Health Children’s is working to make this therapy safer and more beneficial.
Fortunately, Jillian didn’t experience these effects.
“She did fantastic,” said Lee. “She had a low-grade fever but otherwise was fine. It’s a stark contrast to what kids usually experience from high-dose chemo.”
When Jillian returned just 4 weeks later for her check-up, there was no detectable disease. The cancer was gone, and she remains in remission.
Next Steps for CAR T
For families battling childhood cancer, replacing traditional chemotherapy alone with a strategy that combines reduced intensity chemotherapy to lessen disease burden and a one-time infusion of CAR T cells would be revolutionary. In particular, trading long hospital stays for outpatient monitoring, which is possible with CAR T treatment.
Unfortunately, while chemotherapy saves lives, it also comes with many side effects. The immediate side effects, like nausea, hair loss, and susceptibility to illness are well-known and experienced by adults as well. But because of their developmental stage, children have additional challenges.
Late effects, those that emerge years after treatment, are experienced by 2 out of 3 childhood cancer survivors. These can include:
- Learning difficulties
- Growth problems
- Vision changes
- Bone problems
- Hearing loss
- Thyroid problems
- Heart complications
- Dental problems
- Infertility
“As effective as conventional chemotherapy is at treating ALL, it has a lifelong impact,” says Engel. Engel and Lee welcome the day when CAR T cells and reduced intensity therapy become the standard-of-care treatment, especially for children.
In addition to pediatric CAR T clinical trials, UVA Health Children’s conducts basic and translational research in pediatric cancer and CAR T to expand use cases and make this therapy safer for patients. With these clean manufacturing processes and continuing innovations Engel and Lee hope CAR T products will be available off the shelf for patients with cancer.
Committing to Caring Through Treatment
“UVA Health Children’s has a commitment to the elements required to execute this therapy safely,” says Lee. “That means we can perform these treatments for patients here, so they don’t have to travel far to get this kind of care. We have expertise as well as resources like housing and transportation assistance to make receiving care as easy as possible for families.”
“Lots of places can provide great care, but it’s another thing to feel cared for while treatment is happening,” says Engel. “Our team believes in the caring aspect as much as the medical care. Both matter. Families can have great experiences when they have both of those things simultaneously. We're committed to achieving both.”