Figure 6
From: Optimal design, anti-tumour efficacy and tolerability of anti-CXCR4 antibody drug conjugates
Tolerability of lead anti-CXCR4 ADCs in mice inversely correlates with ADC binding strength and lead ADCs present limited toxicity profile. (a) Dosing schedule and time of necropsy during tolerability/safety studies in WT and HuCXCR4KI. Unscheduled necropsies of HuCXCR4KI were due to lack of tolerability to indicated ADC/dose combination. (b–d) Haematology analysis (necropsy day for each treatment group indicated in parenthesis on x-axis), grey bars (N = 3/group, unscheduled necropsies on days 11 and 30), black bars (N = 6/group, scheduled necropsy on day 46). Error bars = standard error of the mean, n.s. = non-significant, *P < 0.02 (One-way ANOVA with Tukey’s multiple comparisons test at day 46). (e–g) Enumeration of haematopoietic progenitors in femur bone marrow, SEM = standard error of the mean. All analyses from same samples, N = 5/group, two-way ANOVA with Dunnett’s multiple comparisons test (e) *P = 0.01, **P = 0.003, ****P = 0.0001. (f) **P = 0.009. (g) **P = 0.009. (h,i) Each symbol represents data from an individual mouse, one-way ANOVA with Tukey’s multiple comparisons test. (h) Proliferation of erythroid progenitors in bone marrow of HuCXCR4KI in homeostatic conditions, all group comparisons with ****P < 0.0001, except pro-erythroblasts versus ortho-erythroblasts: **P = 0.006. (i) Cell surface CXCR4 levels in erythroid progenitors in bone marrow of HuCXCR4KI in homeostatic conditions, all group comparisons with ****P < 0.0001, except where indicated n.s. (non-significant). (e,h,i) baso-erythroblasts = basophilic erythroblasts, poly-erythroblasts = polychromatic erythroblasts, ortho-erythroblasts = orthochromatic erythroblasts.
