Early Lineage T-cell Enrichment Can Help to Improve and Expand the Use of Engineered T-cell Immunotherapies for Children with B-cell Malignancies

Researchers at the Center for Childhood Cancer Research have successfully used engineered T cell immunotherapies to treat pediatric patients with several B-cell malignancies including acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL).  Sometimes, however, in vitro expansion of T cell populations required for these treatments has been problematic, limiting the use of T cell immunotherapies as a treatment option for children with B-cell malignancies.

Clinical studies with newly diagnosed children with ALL and NHL showed that patients with T cell populations containing large numbers of early lineage T cell subtypes (naïve and stem central memory cells) expanded better in vitro than patient T cell populations not enriched with those cell subtypes. Also, early lineage cells were selectively depleted in T cell populations from pediatric patients treated with conventional chemotherapy. The addition of interleukin-7 (IL-7) and IL-15 (IL-15) to patient T cell cultures enriched certain early lineage cells and rescued T cell expansion capability. Other studies demonstrated that patients with ALL had higher numbers of early lineage cells and greater expansion capability than T cells from patients with NHL.

The results from these studies demonstrated that early lineage cells are essential for T cell fitness for expansion and enrichment of these populations—either by timing of T cell collection (prior to chemotherapy) or culture method—can increase the number of patients with B cell malignancies who may be eligible for treatment with engineered T cell immunotherapies.

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