Figure 5
From: Optimal design, anti-tumour efficacy and tolerability of anti-CXCR4 antibody drug conjugates
Efficacy studies with MOLP-8-derived xenografts (SoC- and CXCR4 antibody- resistant MM cell line) to select ADC Fc format and determine ADC MED. (a) Attachment sites of linker-payload on antibody constant regions of light (tags F, F’) and heavy chains (tags C and C’) in DAR4 ADCs 712 and 714. (b) Attachment sites of linker-payload on antibody constant regions of heavy chains (tags C and C’ and sites G and G’) in DAR4 ADCs 711 and 713. The N297A mutation to generate sites G and G’ leads to Fc deglycosylation and reduced effector function. (a,b) LP = linker payload. (c,d) Assessment of Fc format. (e,f) Determination of MED for ADCs 711 and 713. (c,e) Kinetics of orthotopic tumour growth, with a single ADC dose administered at day 8 (arrow indicates dosing day), N = 5/group, SEM = standard error of the mean, (c) **P = 0.006 and ****P < 0.0001, (e) n.s. = non-significant, two-way ANOVA with Tukey’s multiple comparisons test. (c) Fc (+) = active Fc-mediated effector function, Fc (−) = reduced Fc-mediated effector function. (d,f) Kaplan-Meier analysis of median survival.
