Fig. 3: UCART123 targets AML cells in vivo and results in improved overall survival in patient-derived xenografts (PDX) model.
From: Allogeneic TCRαβ deficient CAR T-cells targeting CD123 in acute myeloid leukemia
a Schematic representation of the experimental procedure for the AML- PDX models (AML2 and AML37), showing that animals were treated with PBS, Ara-C, TCRαβ KO T cells or UCART123. Leukemia and T cells in peripheral blood (PB) or bone marrow (BM) were monitored starting on day 2 and later every 2–3 weeks and overall survival was evaluated. b, c Survival curves of PDX-AML2 cohorts treated with 1 × 106 UCART123 (n = 7), 2.5 × 106 UCART123 (n = 15) TCRαβ KO (n = 15), Ara-C (n = 15) or PBS (control; n = 14), and of PDX-AML37 cohorts treated with 2.5 × 106 UCART123 (n = 7) TCRαβ KO (n = 6), Ara-C (n = 5), or PBS (control; n = 5). Treatment with UCART123 significantly prolonged overall survival in PDX-AML2 (b) and PDX-AML37(c) compared to those in control, Ara-C, or TCRαβ KO. UCART123 1 × 106 or 2.5 × 106 vs Ara-C; **** p < 0.0001, UCART123 2.5 × 106 vs TCRαβ KO; ***p = 0.0002, UCART123 2.5 × 106 vs Ara-C; * p = 0.0171, log-rank test. d NPM1 mutant in AML cells and UCART123 transcripts in PB were monitored by ddPCR on day 2 and every 2–3 weeks until mice are dead or killed due to sickness. The ddPCR plot shows simultaneous detection of human ABL1, mouse ABL1, NPM1 mutant, and UCART123 transcripts (left column). Representative examples are shown for a mouse that relapse (top) and one mouse that remained disease free (bottom). Evaluation of leukemia blasts and UCART123 cells in PB and BM at end of study on day 221 by flow cytometry demonstrated one mouse with progression of disease due to loss of UCART123 (top right) and another mouse in remission with sustaining UCART123 (bottom right). Source data are provided as a Source Data file.
