ArticleProceedings of the National Academy of Sciences of the United States of America2025
Generation of actionable, cancer-specific neoantigens from KRAS(G12C) with adagrasib.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
5 citing papers in PubMed, 1 synthesis or guideline pooled it.
- KRAS G12C inhibitors in KRASFrontiers in immunology · 2026Pooled it
- Review
- Expanding the repertoire of chemically induced covalent neoantigens.Nature chemical biology · 2026Article
- RAS signaling at the crossroads of radioresistance and tumor immunity.Journal for immunotherapy of cancer · 2026Review
- Engineered antibodies that stabilize drug-modified KRASNature communications · 2025Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
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 generalize to another FDA-approved KRAS(G12C) inhibitor, adagrasib, whose chemical structure and cysteine reactivity differ substantially from sotorasib. We developed antibodies selective to adagrasib-KRAS(G12C) peptides presented by HLA-A*03 and A*11 that also show cross-reactivity to other KRAS(G12C) inhibitors presented in the same manner. Cryoelectron microscopy structures revealed a mode of adagrasib-peptide/HLA recognition distinctly different from that of sotorasib-directed HapImmune antibodies. The antibodies in a bispecific T cell engager format killed adagrasib-resistant lung cancer cells upon adagrasib treatment. These results support the broad applicability of the HapImmune approach for creating actionable cancer-specific neoantigens and offer candidates for therapeutic development.
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