Fig. 3: Pharmacokinetic profiles and toxic activities of PCMdt-MMAE in mice.
Analysis of PCMdt-MMAE PK profiles: Athymic nude mice (8-week-old) were divided into tumor-bearing (a) and tumor-nonbearing (b) groups (three animals per group). Mice from the tumor-bearing group were subcutaneously injected with 1 × 106 BxPC-3 cells. When tumor volumes reached ~500 mm3, both groups of mice were administered once through the tail vein with 3 or 10 mg/kg of PCMdt-MMAE. Blood samples were collected from individual mice at different time intervals. The amount of MMAE-conjugated PCMbs-MR in plasma was determined by using a MMAE ADC ELISA kit (Eagle Biosciences Inc., Nashua, NH, USA). The PK parameters were calculated using the WinNonlin software package (Certara, Princeton, NJ, USA) [32,33,34]. c Toxic effects of PCMdt-MMAE in vivo: Effects of multiple doses of PCMdt-MMAE on mouse bodyweight were determined by a single administration of PCMdt-MMAE at 10, 30, and 60 mg/kg, respectively. The mice were weighed and monitored for 12 days. The average bodyweight before PCMdt-MMAE injection was 19.8 ± 3.6 g (five mice per group) and set as 100%. ADC, antibody–drug conjugate; MMAE, monomethyl auristatin E; PCMdt-MMAE, monomethyl auristatin E was conjugated to PCMbs–MR to generate the dual-targeting ADC; PCMbs-MR humanized bispecific monoclonal antibody specific to both MET and RON, PK pharmacokinetic
