In head-to-head comparisons, EGFR-targeting Ctx-DDCs outperformedCtx-based ADCs in terms of lysosomal trafficking and cytotoxicity.Tumor selectivity was conferred by the high-affinity Ctx arm, as LDLR-targeting alone exhibited weak activity.DDCs exhibited minimal toxicity to cells without EGFR expression,further highlighting that DDC specificity stems from the tumor antigen-bindingdomain. Here, EGFR is linked to neoplasm.