Results of a study using single-cell RNA sequencing to characterize T cells from patients with cancer and healthy donors, presented at the Society for Immunotherapy of Cancer (SITC) Annual Meeting 2019 in National Harbor, Maryland, showed marked heterogeneity in the T cells derived from patients with chronic lymphocytic leukemia (CLL).

Potential impairment in the baseline functionality of T-cell populations in patients with some relapsed/refractory cancers, such as CLL, compared with T-cell populations from healthy donors, may have an impact on the performance of autologous chimeric antigen receptor T-cell (CAR-T) therapy prepared from the T cells of patients with these cancers.  

This study used in vivo and in vitro assays of T-cell function, as well as single-cell RNA sequencing, to characterize T cells from patients with certain cancers, including CLL, and healthy donors, and to investigate “both gene expression and population differences associated with CAR-T cell performance.”

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Specifically, single-cell transcriptome analysis was used to investigate whether potential differences in the activation mechanisms of the 2 populations of T cells were reflected in molecular features of unmodified (ie, starting material) T cells and CAR-T cells derived from the T cells of both patients with cancer (eg, CLL) and healthy donors.

Notable findings of this study included impaired functionality of CAR-T cells derived from patients with cancer compared with healthy donors, as well as a high degree of heterogeneity in populations of T cells in starting material and CAR-T cells derived from patients with cancer observed.

In their concluding remarks, the study authors noted that the results of their analysis “has allowed us to associate distinct cellular subpopulation and gene expression profiles with preclinical functional outputs.”

Reference

Padalia Z, Karagiannis K, Mcewan B, et al. Single-cell RNA sequencing and functional assessment of healthy donor- and cancer patient-derived T and CAR-T cells.  Poster presented at: the 34th Annual Meeting & Preconference Programs of the Society for Immunotherapy of Cancer 2019 Annual Meeting (SITC 2019); November 6–10, 2019: National Harbor, Maryland. Abstract P187.