Figure 5.

Payload location does not influence in vitro potency of aldehyde-tagged α-HER2 ADCs against NCI-N87 target cells. NCI-N87 cells, which overexpress HER2, were used as targets for in vitro cytotoxicity in a 6 day assay. Free maytansine (gray line) was included as a positive control, and an isotype control ADC (orange line) was used as a negative control to indicate specificity. α-HER2 HIPS-Glu-PEG2-maytansine ADCs bearing the aldehyde tag on the light chain (LC, green), or on the CH1 (red) or C-terminal (CT, blue) regions of the heavy chain showed comparable activity. α-HER2-DM1 was included as a comparator. IC₅₀ values (reflecting the antibody concentrations except in the case of the free drug) were measured as follows: free maytansine, 214 pM; isotype control ADC, could not be determined; LC ADC 87 pM; CH1 ADC, 132 pM; CT ADC 114 pM, α-HER2-DM1, 54.7 pM.