biostudies-literatureMaso LHHS | NIH | National Cancer InstituteNCI NIH HHSHHS | NIH | National Cancer Institute (NCI)e2509012122https://www.ebi.ac.uk/biostudies/studies/S-EPMC12337345biostudies-literatureUnknown122(31)Effective immune therapy against cancer ideally should target a cancer-specific antigen, an antigen that is present exclusively in cancer cells. However, there is a paucity of cancer-specific antigens that are endogenously produced. HapImmune™ technology utilizes covalent inhibitors directed to an intracellular cancer driver to create cancer-specific neoantigens in the form of drug-peptide conjugates presented by class I MHC molecules. Our previous study with sotorasib, an FDA-approved covalent inhibitor of KRAS(G12C), demonstrated that drug-treated cells produce such neoantigens and can be killed by T cell engagers directed against the drug-peptide/MHC complex. Thus, this technology can unite targeted and immune therapies. In the present study, we examined whether this approach could geneProceedings of the National Academy of Sciences of the United States of AmericaGeneration of actionable, cancer-specific neoantigens from KRAS(G12C) with adagrasib.PMC12337345R21CA267362P30CA016087P30 CA016087R01 CA248896R01CA248896R21 CA267362Rajak EKoide AHu ZHattori TNeel BGKoide SMaso LfalseGeneration of actionable, cancer-specific neoantigens from KRAS(G12C) with adagrasib.Effective immune therapy against cancer ideally should target a cancer-specific antigen, an antigen that is present exclusively in cancer cells. However, there is a paucity of cancer-specific antigens that are endogenously produced. HapImmune™ technology utilizes covalent inhibitors directed to an intracellular cancer driver to create cancer-specific neoantigens in the form of drug-peptide conjugates presented by class I MHC molecules. Our previous study with sotorasib, an FDA-approved covalent inhibitor of KRAS(G12C), demonstrated that drug-treated cells produce such neoantigens and can be killed by T cell engagers directed against the drug-peptide/MHC complex. Thus, this technology can unite targeted and immune therapies. In the present study, we examined whether this approach could gene2025-01-01T00:00:00Z2025 Aug2026-06-16T07:08:51.893Z2026-06-16T03:09:41.93ZS-EPMC123373454073732210.1073/pnas.2509012122