Fig. 3: MT-SLP-76 overcomes antigen-low escape in vivo.
a, Mice were treated with 6 × 106 CD22-4-1BBζ CAR T cells ± MT-SLP-76 or control cells (expressing MT-SLP-76 only) 3 days after inoculation with 1 × 106 Nalm6-CD221,300 cells. Shown is the quantification of tumor progression for each individual mouse as measured by photon flux values determined by bioluminescence imaging (BLI); n = 5 mice per group. b,c, Representative bioluminescence images (b) and survival curves (c) of mice treated as in a. Data in a–c are representative of four independent experiments with different T cell donors. d, Percentage of CD22 CAR T cells detected by flow cytometry in the bone marrow of mice treated as in a on days 8 and 16 after treatment; n = 5 mice per group. e, Mice were treated with 1 × 106 CD19-4-1BBζ CAR T cells ± MT-SLP-76 or control cells 3 days after inoculation with 1 × 106 million Nalm6-CD1920,100 (wild-type Nalm6) cells. Shown is the quantification of tumor progression for each individual mouse as measured by photon flux values determined by BLI; n = 5 mice per group. f, Survival curves of mice treated as in e. g, Mice were treated with 7 × 106 CD19-4-1BBζ CAR T cells ± MT-SLP-76 cells 3 days after inoculation with 1 × 106 Nalm6-CD1920,100 cells. Twenty-one days after treatment, spleens were collected, and CAR T cell persistence was assessed by flow cytometry. Data are shown as mean ± s.e.m. of n = 4 mice. h,i, Representative flow cytometric plots (h) and quantification (i) of CAR T stem cell memory T (TSCM) cells (CD62L+CD45RA+), central memory T (TCM) cells (CD62L+CD45RA−), effector memory T (TEM) cells (CD62L−CD45RA−) and terminal effector memory T (TEMRA) cells (CD62L−CD45RA+); n = 4 mice per group. j, Mice were treated with 5 × 106 CD19-CD28ζ CAR T cells ± MT-SLP-76 3 days after inoculation with 1 × 106 Nalm6-CD1920,100 cells. Absolute CAR T cell numbers in the spleen were measured by flow cytometry on days 5, 8, 12 and 28 after treatment (n = 4 mice per time point). Statistical comparisons were performed using repeated-measures two-way analysis of variance (ANOVA) with correction for multiple comparisons (a and e), pairwise log-rank tests without correction for multiple comparisons (c and f), two-way ANOVA (i) or Mann–Whitney test (two-tailed; d, g and j); NS, not significant.
