Integrative single-cell multi-omics of CD19-CAR^pos and CAR^neg T cells suggest drivers of immunotherapy response in B cell neoplasias.

ABSTRACT: The impact of phenotypic, clonal, and functional heterogeneity of chimeric antigen receptor (CAR)-T cells on clinical outcome remains understudied. Here, we integrate clonal kinetics with transcriptomic heterogeneity resolved by single-cell omics to interrogate cellular dynamics of non-transduced (CAR^neg) and transduced (CAR^pos) T cells, in the infusion product (IP) and at the CAR-T cell expansion peak in five B cell acute lymphoblastic leukemia (B-ALL) patients treated with CD19CAR-T cells (varni-cel). We identify significant differences in cellular dynamics in response to therapy. CAR^pos T cells at IP of complete response patients exhibit a significantly higher CD4:CD8 ratio, validated in a larger cohort B-ALL patients (n = 47). Conversely, at the expansi

SUBMITTER: Guerrero-Murillo M 

PROVIDER: S-EPMC11604525 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature