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Single-Cell Decoding of the Clinical Outcome-Associated Diversification and Dynamic Changes of CAR-T Cells in Patients with B-cell ALL

ABSTRACT: Cellular evolution and molecular programs of chimeric antigen receptor-engineered (CAR)-T cells post-infusion are pivotal for developing better treatment strategies. Here, we constructed a high-precision single-cell transcriptional dynamic landscape of 7,578 CAR-T cells from 26 B-ALL patients and evaluated their long-term therapeutic efficacy. We demonstrated that the cytotoxic profile rather than memory property was a favorable biomarker for long-term remission. At the single-cell resolution, we uncovered the vast heterogeneity of CAR-T cells in vivo and identified eight CAR-T cell subtypes. Remarkably, the dominance of cytotoxic subtypes was coincident with long-term remission, while the emergence of subtypes with B-cell transcriptional features could be detected early and predict relapse. Furthermore, we defined transcriptional hallmarks of distinct CAR-T cell populations and revealed molecular changes along computationally-inferred cellular evolution of CAR-T cells in vivo . Collectively, these results illuminated intrinsic properties for durable response and provided molecular cues for improving CAR-T immunotherapy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE162975 | GEO | 2023/10/26

REPOSITORIES: GEO

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