Project description:Murine chimeric antigen receptor transduced T cells (CAR-T cells) deficient in perforin recapitulate hemophagocytic lymphohistiocytosis (HLH)-like toxicities occuring in human CAR-T recipients. We used microarray to describe gene expression profiles of wild-type and perforin-deficient CAR-T cells.
Project description: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.
Project description:Interventions: experimental group:CD276-targeted chimeric antigen receptor T cells
Primary outcome(s): SAE rate
Study Design: Single arm
