Integrative single-cell multi-omics of CD19-CARpos and CARneg T cells suggest drivers of immunotherapy response in B-ALL

Despite initial high-rates of complete response, <50% of B-cell acute lymphoblastic leukemia (B-ALL) patients treated with CD19-directed chimeric antigen receptor (CAR)-T cells maintain durable remissions. We integrated clonal kinetics and genetic heterogeneity with single-cell-TCR sequencing and single-cell-RNA sequencing, respectively, to explore the cellular dynamics response of both non-transduced (CARneg) and transduced (CARpos) T-cells. CARneg and CARpos T-cells were longitudinally interrogated in the manufactured infusion product (IP) and in peripheral blood at the time of CAR-T cell expansion peak following infusion in five adult B-ALL patients treated with CD19CAR-T products. Overall design: scRNAseq and scTCRseq data of 5 patients treated with CD19CAR-T products. For each patient there is sequenced data with transducted (CARpos) and non-transducted data (CARneg) from the infusion product and the peak of expansion (in vivo).