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Younger T Cells May Improve Immunotherapy for Pediatric Cancer

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Key Points

  • The study team found that early-lineage T cells, classified as either naive T cells or stem central memory T cells, were the most effective in immunotherapy, and expanded best in the laboratory setting.
  • Early-lineage T cells were more vulnerable to chemotherapy than older cells.
  • Adding the signaling proteins interleukin-7 and interleukin-15 to T cell cultures expanded stem central memory cells in samples from both ALL and NHL patients.

Pediatric oncologists from The Children’s Hospital of Philadelphia (CHOP) have investigated techniques to improve and broaden a novel personalized cell therapy to treat children with cancer. The researchers say that a patient’s outcome may be improved if clinicians select specific subtypes of T cells to attack diseases like acute lymphoblastic leukemia (ALL) and lymphoma. Their findings were published by Singh et al in Science Translational Medicine.

“Our main finding is that younger T cells are critically important in T cell immunotherapy,” said David M. Barrett, MD, PhD, a pediatric oncologist at CHOP. “Collecting and expanding these cells could increase the number of children with cancer who could benefit from this innovative treatment.”

The T cell therapy, developed by Dr. Barrett and Stephan A. Grupp, MD, PhD, along with collaborators at the Perelman School of Medicine at the University of Pennsylvania, is a form of immunotherapy. Specifically, the scientists modify T cells, the workhorses of the body’s immune system, to attack B cells, other immune cells that become cancerous in specific cancers such as ALL. The researchers first extract a patient’s own T cells and reprogram them to hunt down and eliminate B cells after those modified T cells are returned to the patient.

Dr. Barrett and colleagues followed 50 child and adolescent patients in a clinical trial of B-cell cancers at CHOP, of whom 38 had ALL and 12 had non-Hodgkin’s lymphoma (NHL). The study team measured immune system markers and fully characterized their T cell populations once a month for 6 months following a patient’s initial diagnosis.

Study Findings

Scientists already knew that T cells evolve after they become active, but the current study fully characterized the T cell subtypes in the context of cell therapy. The study team found that early-lineage T cells, classified as either naive T cells or stem central memory T cells, were the most effective in immunotherapy. Those early-lineage T cells also expanded best in the laboratory, before they were returned to each patient for T cell therapy.

Significantly, early-lineage T cells were also more vulnerable to chemotherapy than older cells.

These findings, said Dr. Barrett, have the potential to change clinical management in T cell immunotherapy. “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,” he said. “We could keep the patient’s early-lineage T cells in reserve, in case the patient needs them later.”

In addition, the study team showed that adding the signaling proteins interleukin-7 and interleukin-15 to T cell cultures expanded stem central memory cells in samples from both ALL and NHL patients.

Finally, the study team found that ALL patients had a different mixture of T cell subtypes than did NHL patients. ALL patients had higher levels of early lineage T cells, with greater expansion potential, than did NHL patients. Dr. Barrett added that further research should focus on improving outcomes for children with NHL.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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