Antibody-Drug Conjugates Targeting the EGFR Ligand Epiregulin Elicit Robust Antitumor Activity in Colorectal Cancer.

ABSTRACT: As colorectal cancer remains a leading cause of cancer-related death, identifying therapeutic targets and approaches is essential to improve patient outcomes. The EGFR ligand epiregulin (EREG) is highly expressed in RAS wild-type (WT) and mutant colorectal cancer, with minimal expression in normal tissues, making it an attractive target for antibody-drug conjugate (ADC) development. In this study, we produced and purified an EREG mAb, H231, which had high specificity and affinity for human and mouse EREG. H231 also internalized to lysosomes, which is important for ADC payload release. ImmunoPET and ex vivo biodistribution studies showed significant tumor uptake of zirconium-89-labeled H231, with minimal uptake in normal tissues. H231 was conjugated to either cleavable dipeptide or tripepti

SUBMITTER: Jacob J 

PROVIDER: S-EPMC11875910 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature