Multiomics profiling shows heterogeneities in profiles of donor and patient CAR T cells

Bai Z, Lundh S, Kim D, et al. Single-Cell Multiomics Dissection of Basal and Antigen-Specific Activation States of CD19-Targeted CAR T Cells. Journal for ImmunoTherapy of Cancer. 2021; 9 (5) (doi: 10.1136/jitc-2020-002328).

The cellular and molecular states of autologous chimeric antigen receptor (CAR) T cells are markedly unlike those of allogeneic CAR T cells — differences researchers say could help explain disappointing results in some cancer patients treated with the latter. Autologous T cells targeting CD19 have been highly effective against refractory leukemia and lymphoma, for example, but patients treated with engineered cells generated from healthy donors often do not benefit at all or eventually relapse. Seeking more insight, investigators used single-cell multiomics technology and canonical signaling pathway analysis to identify properties of CAR T cells from healthy donors and properties of CAR T cells from patients with acute lymphoblastic leukemia. The work exposed transcriptional, phenotypic, functional, and metabolic disparities between basal CD19-targeted CAR T cells and CAR T cells after antigen-specific activation. The finding that CAR T cell behavior hinges on whether cells are derived from patients or whether they originate from healthy donors has significant implications for immunotherapy going forward. The evidence, the study authors write, provides a "mechanistic basis for ameliorating clinical outcomes and developing next-generation 'off-the-shelf' allogeneic products."

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