Early Lineage T Cells Are Better for Immunotherapy in Pediatric Patients With ALL and Lymphoma

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Early Lineage T Cells Are Better for Immunotherapy in Pediatric Patients With ALL and Lymphoma
Early Lineage T Cells Are Better for Immunotherapy in Pediatric Patients With ALL and Lymphoma

Outcomes from a novel personalized cell therapy may be improved if specific subtypes of T cells are selected to attack diseases such as acute lymphoblastic leukemia (ALL) and lymphoma.1

"Our main finding is that younger T cells are critically important in T cell immunotherapy," said pediatric oncologist David M. Barrett, MD, PhD, at The Children's Hospital of Philadelphia (CHOP) in Pennsylvania. "Collecting and expanding these cells could increase the number of children with cancer who could benefit from this innovative treatment."

Barrett collaborated with Stephan A. Grupp, MD, PhD, and Jessica Perazzelli, both of CHOP; and Nathan Singh, MD, a resident in the Perelman School of Medicine at the University of Pennsylvania, and first author of the study. Grupp has received national attention for his work in using reprogrammed T cells to treat children with relapsed or refractory ALL. The current research reports on insights and laboratory techniques that may advance this treatment.

This study uses T cell therapy, which is a form of immunotherapy in which the body's own immune system is manipulated into serving as the treatment. In specific cancers, such as ALL, B cells become cancerous; this type of immunotherapy modifies T cells to attack those cancerous B cells. First, researchers extract a patient's own T cells, then reprogram them to find and attack B cells, and the reprogrammed T cells are returned to the patient's body.

This study 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 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.

This study fully characterized the T cell subtypes that evolve in the context of cell therapy. The researchers found that early lineage T cells, classified as either naive T cells (newly minted cells) or stem central memory T cells (self-renewing, highly proliferative 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.

So, enriching T cell populations for early lineage cells should be a fruitful approach. Barrett said that these findings may 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."

The study also found that the mixture of T cell subtypes differed between patients with ALL and those with NHL.


1. Singh N, Perazzelli J, Grupp SA, Barrett DM. Early memory phenotypes drive T cell proliferation in patients with pediatric malignancies [published online ahead of print January 6, 2016]. Sci Transl Med. 2016;8(320):320ra3. doi:10.1126/scitranslmed.aad5222.

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