Effects of Mutations on MUC1-C/ED Protein Stability and Antibody Binding: Structural Insight

Overview

MUC1-C is a transmembrane oncoprotein overexpressed in pancreatic and other cancers, and its extracellular domain (ED) is a target for antibody-drug conjugate (ADC) therapeutics. This project used structural and computational analysis to understand how specific mutations affect MUC1-C/ED protein stability and antibody binding — information that directly informs ADC epitope and design choices.

The work fed into a related preclinical study demonstrating systemic metabolic reprogramming and marked tumor regression in pancreatic cancer models treated with a MUC1-C–targeted ADC (currently under review at Molecular Cancer Therapeutics). My contribution to that study included the metabolomics analysis arm — comparing untargeted LC-MS metabolite profiles across control, antibody-only, and ADC-treated groups to characterise the metabolic reprogramming induced by MUC1-C–targeted treatment.

Key Highlights

• Structural interpretation of MUC1-C/ED mutation effects on stability and folding
• Computational assessment of antibody-binding consequences for ADC epitope design
• Directly supports a MUC1-C–targeted ADC program for pancreatic cancer
• Published in Biochemical and Biophysical Research Communications (IF 3.4)
• Untargeted LC-MS metabolomics analysis of ADC-treated pancreatic cancer models
• Related preclinical efficacy study under review at Molecular Cancer Therapeutics (IF 6.9)