Inhibition of ERAP1 upregulates and creates novel neoantigens, resulting in improved immunogenicity, generation of CD8+ T cell responses and tumour growth inhibition. Grey Wolf is developing novel, first-in-class ERAP1 inhibitors that upregulate immunogenic neoantigens at the tumour cell surface and can be recognised by the immune system.

The Antigen Presentation Pathway

Hover over each of the interactive dots to learn more about the antigen presentation pathway

Cellular proteins

  • Multiple sources of protein that feed the antigen presentation pathway.

Proteasome

  • The majority of peptides that feed the antigen presentation pathway are degraded by the proteasome.

Peptides

  • Peptides generated by the proteasome are transported into the ER.

TAP

  • Peptides from the cytosol are transported into the ER via the TAP transporter complex.

ERAP1 and ERAP2

  • ER resident aminopeptidases which trim or over-trim antigens and neoantigens prior to loading onto MHC Class I. ERAP1 and ERAP2 have different peptide specificities.

MHC Class I and CD8 T cells

  • At the cell surface the MHC Class I complex presents antigens / neoantigens to CD8 T cells where they are recognised as ‘self’ or 'non-self’.

MHC Class I

  • Peptides loaded onto the MHC Class I complex through the action of the Peptide Loading Complex (PLC) and ERAP1/2 activity are transported to the cell surface.