Figure 6
A7R-ADC eliminates steroid-resistant IL-7R-positive lymphocytes in physiological bone marrow and spleen or autoimmune arthritis. (a) Changes in cell numbers in response to A7R-ADC-SN-38 treatment (0.6 mg/kg as an equivalent SN-38 dose) or high-dose DEX (10 or 40 mg/kg) at 7 days after injection. Each bar represents the mean ± SD (n = 3). (b) Drug design of anti-IL-7R ADC with MMAE. MMAE was conjugated to an anti-IL-7R monoclonal antibody (A7R) via a Val-Cit linker. (c) Kinetics of arthritis scores in mice with collagen antibody-induced arthritis (CAIA) were evaluated using saline as a control, the TNF inhibitor etanercept (ETA, 30 mg/kg), DEX (10 mg/kg), free MMAE (0.6 mg/kg), control ADC with MMAE (CTR-MMAE, 30 mg/kg) or A7R-ADC-MMAE (A7R-MMAE, 30 mg/kg, both ADCs; 0.6 mg/kg as an equivalent MMAE dose) (n = 5). P < 0.01 (saline vs. ETA; A7R-MMAE vs. CTR-MMAE; DEX vs. CTR-MMAE), P <  0.001 (saline vs. DEX or A7R-MMAE; A7R-MMAE vs. ETA or free-MMAE; DEX vs. ETA or free-MMAE). Bar = SD. (d) Comparison of joint histology in mice with CAIA treated with saline, DEX and A7R-MMAE. H.E., hematoxylin and eosin staining. (e) Immunohistochemical staining of IL-7R in the inflammation site of CAIA compared with that in mice treated with saline, DEX and A7R-MMAE. Top, IL-7R-positive cells (green); bottom, optical image.
