Small molecule inhibitors enhancing tumor immunogenicity by modulating antigen processing

Overview

The University of Athens has developed innovative small molecule inhibitors targeting the enzyme ERAP1 to enhance tumor immunogenicity. These inhibitors aim to reprogram antigen processing and presentation in cancer cells, thereby increasing their antigenicity. This enhancement occurs through three mechanisms: boosting pre-existing immune responses to tumor-associated antigens, inducing responses to novel epitopes, and enhancing NK cell cytotoxicity. By modulating the immunopeptidome, this approach can counteract immunosuppressive tumor microenvironments and complement other immunotherapies, such as CAR T-cell therapies.

Technical specifications

• Target enzyme: ER aminopeptidase 1 (ERAP1)
• Mechanisms of action:
  • Enhances pre-existing responses to tumor antigens
  • Induces novel T-cell responses by restoring cancer epitope presentation
  • Enhances NK cell activity by altering MHC class I recognition
• Validation procedures:
  • In vitro and in vivo model tests
  • Affinity purification and sequencing of MHC class I bound peptides
  • RiboSeq and whole proteome analysis for non-canonical epitopes
  • Evaluation of inhibitor effects on PBMC cytotoxicity and NK cell activation

Technology readiness level

This technology is at TRL 3, having demonstrated proof-of-concept in laboratory settings. Future validation includes comprehensive analyses using both in vitro and in vivo models to assess enhancer effects on the immunopeptidome and synergy with CAR-T therapies.