Wilson TL, Hyunjin K, Chou C-H, et al. Common Trajectories of Highly Effective CD19-Specific CAR T Cells Identified by Endogenous T Cell Receptor Lineages. Cancer Discovery. 2022; (doi: 10.1158/2159-8290.CD-21-1508).
Examining CD19-specific chimeric antigen receptor (CAR) T cell products through single-cell sequencing, instead of assessing them as a collective, exposes common characteristics shared by highly effective cells. Researchers used CD-19 CAR T cells from the blood and bone marrow of children with B cell acute lymphoblastic leukemia to assemble a single-cell gene expression and T cell receptor (TCR) sequencing dataset. Cytotoxic post-infusion cells with like TCRs represented a subset of effector precursor cells whose transcriptional profile differed from other pre-infusion cells. When stimulated, these cells were functionally superior. They also were found to reduce expression of TOX, a transcription factor linked to cell exhaustion. The research points to a range of effector possibilities within pre-infusion CAR T cell products, which can subsequently be exploited and incorporated into treatment approaches.