Article Figures & Data
Figures
- Fig. 1.
Inhibitory activity of ASP7266 against TSLP/TSLPR interaction. (A) Inhibitory activity of ASP7266 against the human TSLP/TSLPR interaction evaluated using competitive ELISA. Data indicate mean ± S.D. for three subjects. Four-parameter logistic curve is shown. (B) Inhibitory effects of ASP7266 and tezepelumab on TSLP-induced proliferation of Ba/F3 cells. Data indicate mean ± S.D. for five subjects. (C) Inhibitory effects of ASP7266 and tezepelumab on CCL17 production in PBMCs. CCL17 measurements were conducted 5 days after stimulation with 5 ng/ml TSLP. Data indicate mean ± S.D. for five or four subjects. Medium, RPMI1640 medium without antibody. Control IgG, isotype control IgG1.
- Fig. 2.
Inhibitory effects of ASP7266 on human TSLP-stimulated human mDC-mediated differentiation of naive CD4+ T cells. (A) Experimental outline. CD4+ T cells cocultured with TSLP-stimulated human mDCs produced inflammatory cytokines after CD3/CD28 stimulation. The concentration of IL-4 (B), IL-5 (C), IL-13 (D), and TNF-α (E) in the supernatant was measured using Multiplex. Horizontal bars indicate the mean of three independent experiments (each symbol) using blood from each subject.
- Fig. 3.
Inhibitory effect of ASP7266 on TSLP-induced IL-5 production in human PBMCs. PBMCs were cultured for 7 days with TSLP, IL-25, and IL-33 or control medium for the no stimulation group. Cells and supernatants were collected for flow cytometry (A) and AlphaLISA (B). (A) Flow cytometric analysis of IL-5 production from lineage-negative cells (inside the box). Representative results from the same experiment are shown. (B) IL-5 protein levels from PBMCs. Data indicate mean ± S.D. for 6 subjects.
- Fig. 4.
Cross-reactivity of ASP7266 with mouse, rat, and monkey TSLPR. (A) Binding of ASP7266 to TSLPR was determined using ELISA. Each data point represents the mean ± S.D. for four subjects. (B) Inhibitory effect of ASP7266 on CCL17 mRNA expression level in human and monkey peripheral white blood cells. Each data point represents the mean ± S.D. for six subjects.
- Fig. 5.
Inhibitory effect of ASP7266 on ascaris extract–induced skin reactions in a monkey model. Monkeys in the normal group (no sensitization) and control group (with sensitization) were administered the formulation buffer instead of ASP7266. The severity of the ascaris-specific skin reaction was determined by subtracting the mean diameter of the PBS-injected site from the mean diameter of the ascaris extract–injected site in each monkey. The horizontal line indicates the mean for six (normal and control group) or five monkeys (ASP7266-treated group). Differences between two groups were compared using an unpaired two-tailed t test. * P < 0.05 vs. normal group, # P < 0.05 vs. control group.
Tables
- TABLE 1
IC50 and IC90 values in TSLP/TSLPR interaction
IC50 and IC90 values were calculated using non–linear regression analysis with reactions with only medium defined as 100% inhibition, and reactions with TSLP without antibody were defined as no inhibition.
Competitive ELISA Ba/F3 Cell Proliferation CCL17 Production by PBMCs IC50 IC90 IC50 IC90 IC50 IC90 ng/ml ng/ml ng/ml ng/ml ng/ml ng/ml ASP7266 208 462 90.7 200 16.1 163 Tezepelumab 33.0 93.8 518 15,300 67.0 855
Data Supplement
- Supplemental Figure -
Pharmacokine tics of ASP7266 in a monkey model.
- Supplemental Figure -
