Innovative Immunotherapy May Improve Outcomes of Children with Leukemia

Researchers from The Children’s Hospital of Philadelphia (CHOP) recently found early lineage T cells are most effective in immunotherapy to treat children with acute lymphoblastic leukemia (ALL).

"Collecting and expanding these cells could increase the number of children with cancer who could benefit from this innovative treatment," said pediatric oncologist at CHOP, David M. Barret, MD, PhD.

Scientists modified the T cells to attack B cells, which become cancerous in ALL. The process includes extracting a patient’s T cells, reprogramming them, and then returning the cells back into the patient.

The study, published in Science Translational Medicine, included a clinical trial of B cell cancers at CHOP using 50 children and adolescents. There were 38 patients diagnosed with ALL and 12 who had non-Hodgkin’s lymphoma (NHL).

Researchers measured immune system markers to characterize patient T cell populations once a month for 6 months after diagnosis.

Although scientists previously knew that T cells evolve after they become active, the current study showed that T cell subtypes were fully characterized in the context of cell therapy.

Researchers also found that early-lineage T cells, classified as naïve T cells or stem central memory T cells, were more effective in immunotherapy and were more vulnerable to chemotherapy compared with older cells. The T cells were also able to expand best in the laboratory setting before being used in each patient for T cell therapy.

"In newly diagnosed patients, it may be preferable to collect their T cells much earlier than currently done, before chemotherapy, or between chemotherapy cycles, instead of after a patient relapses," Barrett said. "We could keep the patient's early-lineage T cells in reserve, in case the patient needs them later."

The researchers were able to show that by adding the signaling proteins interleukin-7 and interleukin-15 to T cell cultures, stem central memory cells were able to expand in ALL and NHL patient samples.

It was also discovered that patients with ALL had a different mixture of T cell subtypes than patients with NHL. Furthermore, ALL patients had both a higher level of early lineage T cells and a greater expansion potential over NHL patients.

In the future, researchers will focus on improving the outcomes for children diagnosed with NHL.