Figure 4.

CD33 chimeric antigen receptor construct (CD33CART) inhibits leukemia proliferation in vivo in childhood acute myeloid leukemia (AML) patient-derived xenograft models. Busulfan-conditioned NSGS mice engrafted with primary AML cells (tertiary PDX models (A) JMML117 and (B) AML290) were randomized (n=5 mice/cohort) to intravenous treatment with saline, irrelevant target GFP-transduced T cells ((-)TC), or one of the CD33CARTs as designated (5×10⁶ total cells/mouse). CD33CART transduction efficiency ranged from 19.9% to 88.3% for these experiments with information detailed in online supplemental table 1. Mice were followed by weekly flow cytometric quantification of human CD33+/CD45 +AML and CD3+ CAR T cells in peripheral blood. Animals were euthanized at 2 or 4 weeks after treatment depending on rate of leukemia progression in control animals or >15% wt loss. AML cells and T cells were quantified in murine bone marrow and/or spleens as above. Superior leukemia clearance was again seen with the lintuzumab-based CD33CART with a CD28/CD3ζendodomain (lin-28z). *P<0.05, **p<0.01, ***p<0.001 by ANOVA with Dunnett post-test for multiple comparisons of treatment group versus saline control (black bars). Absence of symbol indicates lack of statistical significance.