Discovery of molecular glues for modulating MHC presentation of cancer neoantigens

Peptide MHC glues (PMGs) identified via a chemical strategy promote peptide–MHC class I complex formation for otherwise unpresentable cancer antigens, enabling their surface presentation.

• Why it matters: Many cancer-specific antigens do not form Class I MHC complexes and are poorly displayed, limiting cancer immunosurveillance and therapeutic targeting.
• What they did: The study used a chemical approach to identify PMGs and determined crystal structures of peptide–MHC complexes to define how compounds stabilize binding.
• The result: Structures show PMGs stabilize antigen–MHC binding through simultaneous interactions with both the MHC protein and antigen peptides, chemically rewiring Class I presentation and accessing rare antigens.

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